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Abstrak :
Latar Belakang: Penelitian yang dilakukan bertujuan untuk mengetahui secara lebih mendalam mekanisme molekuler fenomena respons adaptasi pada penduduk Mamuju, Sulawesi Barat sebagai area radiasi latar tinggi (high background radiation area/HBRA) di Indonesia khususnya ditinjau dari jalur inflamasi dan stress oksidatif. Metode: Penduduk Dusun Tande-Tande, Mamuju sebagai area radiasi latar tinggi dan penduduk Desa Topoyo, Mamuju Tengah sebagai kelompok kontrol direkrut dalam penelitian. Pemeriksaan kerusakan DNA, aberasi kromosom tidak stabil, stabil, mikronukleus, indeks mitosis, nuclear division index, aktivitas enzim SOD, GPx konsentrasi CAT serum dan darah lengkap dilakukan pada penelitian. Analisis G2 MN dilakukan untuk memvalidasi respons adaptasi pada penduduk Dusun Tande-Tande. Pengukuran konsentrasi sitokin dan protein pro-inflamasi, anti-inflamasi, p-Akt, Akt, dan NFkB dilakukan untuk mengetahui keterlibatan jalur inflamasi dan stress oksidatif pada fenomena respons adaptasi. Hasil: Analisis kerusakan DNA, aberasi kromosom tidak stabil, stabil, aktivitas SOD, aktivitas GPx menunjukkan tidak terdapat perbedaan yang bermakna antara kedua kelompok penelitian. Rerata konsentrasi CAT kelompok kasus lebih rendah secara bermakna dibandingkan kelompok kontrol. Nilai indeks mitosis dan nuclear division index (NDI) pada kelompok kasus lebih tinggi secara bermakna dibandingkan kelompok kontrol. Rerata konsentrasi sitokin proinflamasi dan anti-inflamasi pada serum kelompok kasus lebih rendah secara bermakna dibandingkan kelompok kontrol. Rerata konsentrasi protein marker inflamasi CRP pada serum kelompok kasus lebih rendah tetapi tidak bermakna secara statistik dibandingkan kelompok kontrol. Hasil pemeriksaan darah lengkap memperlihatkan bahwa jumlah sel darah merah kelompok kasus lebih tinggi secara bermakna sedangkan jumlah limfosit, nilai MCV, MCH, MCHC, dan RDW kelompok kasus lebih rendah secara bermakna dibandingkan kelompok kontrol. Rerata nilai rasio p-Akt/Akt dan konsentrasi NFkB kelompok kasus lebih rendah secara bermakna dibandingkan dengan kelompok kontrol. Kesimpulan: Fenomena respons adaptasi terhadap radiasi terjadi pada penduduk Dusun Tande-Tande, Mamuju. Hasil penelitian belum dapat membuktikan peningkatan antioksidan serta sitokin tertentu baik sitokin pro maupun anti-inflamasi pada kelompok kasus. Aktivasi jalur Akt dan NFkB pada kelompok kasus belum dapat dibuktikan mengingat nilai rasio p-Akt/Akt serta konsentrasi NFkB lebih rendah secara bermakna dibandingkan dengan kelompok kontrol. ......Background: This study aim is to investigate the molecular mechanism of radioadaptive response in inhabitants of Mamuju, West Sulawesi as one of the high background radiation areas of Indonesia, particularly from inflammatory and oxidative stress perspectives. Methods: Tande-Tande sub-village, Mamuju district inhabitants as high background radiation areas, and Topoyo Village inhabitants in Middle Mamuju district were recruited in this study. Evaluation of DNA damage, unstable and stable chromosomal aberrations, micronucleus, mitotic index, nuclear dividon index, SOD and GPx activities, serum catalase concentration and complete blood count were performed in this study. The G2 MN assay for validating the radioadaptive response phenomenon was performed in this study. Measurement of pro and anti-inflamamatory cytokines, p-Akt, AKt and NFkB were performed to find out the involvement of infllmation and stress oxidative on radioadaptive response phenomenon. Results: The levels of DNA damage and stable and unstable chromosomal aberrations were not significantly different between the two groups. The rate of cell proliferation represented by the mitotic and nuclear dividion indexes showed a significantly higher rate in the case group. The SOD and GPx activities were not significantly different between the two groups. Interestingly, the CAT concentration was significantly lower in the case group. A significant lower level of both pro- and anti-inflammatory cytokines was also found in the case group. A lower level of CRP concentration as an inflammatory marker protein also showed in the present study, although it was not statistically significant. The complete blood counts analysis revealed a significant increase in RBC numbers and a significant decrease in lymphocyte numbers (MCV, MCH, MCHC, and RDW values) in the case group. The p-Akt/Akt ratio and NFkB concentration were also found to be statistically lower in the case group. Conclusion: It can be concluded that the radioadaptive response phenomena induced by chronic low radiation dose exposure existed in Tande-Tande sub-village inhabitants. However, this present study failed to find a significant increase of antioxidant enzymes and inflammatory cytokines in Tande-Tande sub-village inhabitants. The activation of Akt and NFkB pathways in Tande-Tande sub-village inhabitants was also not found in this present study.

Abstrak :
Pendahuluan: Prevalensi penyakit kanker payudara di Indonesia terus meningkat. Keberhasilan terapi kanker saat ini tidak lepas dari efek samping serta biaya yang tinggi, sehingga mendorong eksplorasi bahan alam yang berpotensi antikanker. β-glukan dari jamur tiram (Pleurotus ostreatus) berpotensi sebagai anti kanker melalui sifatnya sebagai imunostimulator. Tujuan penelitian ini yaitu menganalisis aktivitas imunostimulasi dan anti proliferasi β-glukan pada tikus Sprague-Dawley yang diinduksi kanker payudara dengan DMBA. Metode: Tikus dibagi dalam 7 kelompok yang terdiri atas kelompok normal (5 ekor) dan 6 kelompok perlakuan yang diinduksi DMBA (8 ekor per kelompok). Kelompok perlakuan terdiri atas kelompok DMBA, kelompok DMBA dengan β-glukan yang diberikan secara preventif dosis 0,25 g/kg BB (P 0,25) dan 1 g/kg BB (P 1,00) selama 28 minggu dan sebagai adjuvan bersama dengan Doxorubicin (10 μg/kg BB) dengan 2 dosis yang sama (A 0,25 dan A 1,00), β-glukan diberikan selama 30 hari. Induksi tumor dilakukan dengan pemberian DMBA per oral dengan dosis 20 mg/kg BB, selama 3 minggu (2x/minggu, total 5x). Hasil: Pemberian β-glukan secara preventif cenderung menurunkan insidensi tumor sebesar 37,5% (P 0,25) dan 50 % (P 1,00) dibandingkan kontrol karsinogen DMBA (87,5 %). Volume total tumor terendah didapatkan pada kelompok P 0,25 (5,3 cm3), sedangkan jumlah total tumor terendah pada kelompok P 1,00 (5 nodul). Penurunan volume total dan jumlah total tumor juga tampak pada kelompok adjuvan. Kelompok A 0,25 memiliki volume total tumor (6,5 cm3) dan jumlah total tumor (8 nodul) terendah. Pemberian β-glukan secara preventif tampaknya memicu pelepasan TNF-α yang diikuti oleh NO dan memberikan hambatan karsinogenesis sehingga menurunkan volume dan jumlah total tumor. Terdapat gambaran Ductal Carcinoma Invasive (DCIV) pada semua kelompok perlakuan dengan rerata skor dan gradasi yang bervariasi, dimana kelompok P 0,25 memiliki rerata skor terendah (2,4). Pemberian β-glukan menghambat proliferasi sel tumor secara bermakna, dengan indeks AgNOR yang terendah pada P 0,25 (1,4 ; p < 0,05), dan A 0,25 (1,6; p <0,05). Ekspresi CD8+ pada kelompok β-glukan lebih rendah daripada kelompok DMBA. Simpulan: β-glukan yang diberikan secara preventif memediasi respon imun antitumor yang diperantarai oleh TNF-α dan NO.

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Introduction: The prevalence of breast cancer in Indonesia continues to increase. Since current therapy of cancer is accompanied by the presesnce of side effects and high costs, exploration of potentially natural anticancer material needs to be encouraged. β-glucan from oyster mushroom (Pleurotus ostreatus) have potency as anti-cancer through its nature as an immunostimulatory. The purpose of this study is to analyze the activity of immunostimulation and anti-proliferation of β- glucan in Sprague-Dawley rats induced breast cancer with DMBA. Methods: Rats were divided into 7 groups: i.e. 1 group of normal/control (5 rats) and 6 groups of DMBA-induced treatment (8 rats each). The treatment group consisted of DMBA and DMBA groups with β-glucan fed, which were given as preventive at dose of 0.25 g/kg-body weight (P 0.25) and 1 g/kg-body weight (P 1.00) everyday for 28 weeks and as adjuvant with doxorubicin (10 μg/kgbody weight) at the same dose (A 0.25 and A 1.00) everyday for 30 days. Cancer induction was conducted by giving DMBA orally at a dose of 20 mg/kgbody weight, for 3 weeks (twice a week, totally 5 times). Results: The result showed decreasing tendency in the incidence of tumors in group P, i.e. 37.5% (P 0.25) and 50% (P 1.00), in comparison with DMBA (87.5%). The lowest total tumor volume was found in group P 0.25 (5.3 cm3), while the lowest total number of tumors were in group P 1.00 (5 nodules). A decrease in the total volume and the total number of tumors was also seen in the adjuvant group. Group A 0.25 has total tumor volume (6.5 cm3) and the total number of tumors (8 nodules) the lowest. Administration of β-glucan preventively seem to trigger the release of TNF-α followed by NO and inhibit carcinogenesis resulting in lower volume and the total number of tumors. Invasive Ductal Carcinoma (DCIV) were found in all treatment groups with varied mean score and gradation, where in group P 0.25 had the lowest mean score (2.4). Administration of β-glucan inhibits tumor cell proliferation significantly, with a low AgNOR index at P 0.25 (1.4; p <0.05), and A 0.25 (1.6; p <0.05). Expression of CD8+ in the group of β-glucans were lower than DMBA group. Conclusion: β-glucan given preventively could favorably modify antitumor immune response mediated by TNF-α and NO.

Abstrak :
ABSTRAK
Pendahuluan :Trypanosoma evansi adalah protozoa berflagella yang bersirkulasi di dalam darah secara ekstraseluler sebagai agen penyakit Surra serta menyerang seluruh hewan vertebrata, serta berpotensi sebagai zoonosis. Informasi virulensi isolat T. evansi sangat dibutuhkan untuk penentuan strategi pengobatan Surra di daerah wabah dan endemis. Penelitian ini bertujuan untuk mengetahui variasi virulensi isolat T. evansi yang dikoleksi dari berbagai wilayah di Indonesia termasuk memperoleh marka genetik serta mengetahui profil sitokin pada mencit. Disamping itu, dilakukan juga uji serologis pada peternak di daerah wabah Surra Metode : Sebanyak 32 isolat lokal T. evansi dikonfimasi dengan PCR multiplex (ITS-1; Te Ro Tat 1,2 VSG dan ESAG6/7), selanjutnya diuji virulensinya dengan menginfeksikan104 parasit pada mencit galur DDY. Studi genotyping populasi T. evansi dievaluasi dengan 8 marka mikrosatelit Tbb-1, Tbb-5, Tbb-9, Tbb-10, MORF2-CA, M6C8-CA, MEST-19AT, MT3033-AT. Dua isolat yang berbeda virulensi (tinggi-Bang87 dan rendah-Pml 287) dipilih untuk uji imunopatogenitas sedangkan serum peternak diuji dengan metode FELISA dan CATT T. evansi. Hasil : Dari 32 isolat tersebut terbagi menjadi 17 isolat bervirulensi tinggi, 11 isolat bervirulensi moderat dan 4 isolat bervirulensi rendah dengan 8 pola tingkat parasitemia. Analisis Neigbour Joining (NJ) terhadap 8 lokus berdasarkan Multi Lokus Genotipe (MLG) mikrosatelit terbagi menjadi 4 populasi, yaitu MLG A, MLG B, MLG C dan MLG D. Analisis terhadap struktur populasi juga memberikan hasil yang sama dengan terbentuknya 4 klaster. Hasil ini juga membuktikan bahwa marka yang digunakan bersifat spesifik lokasi. Sebanyak tiga marka mengindikasikan adanya asosiasi antara virulensi dan MLG (Tbb-1, M6C8-CA dan MEST-19). Kadar IFN-γ meningkat secara tajam pada mencit yang diinfeksi isolat Bang 87 pada 4hpi berkorelasi negatif yang signifikan (p<0,05) dengan kadar IL-10, sedangkan pada mencit yang diinfeksi isolat Pml 287, peningkatan kadar IFNγ berkorelasi positif dengan kadar IL-10. Kematian dini pada mencit yang diinfeksi isolat Bang 87 disebabkan oleh sindrom respon inflamasi sitemik. Hasil uji serologis menunjukkan bahwa 4 dari 24 serum peternak (16,67%) didaerah wabah positif dan seluruh serum negatif untuk daerah non wabah. Kesimpulan : Variasi virulensi T. evansi isolat Indonesia memiliki karakter molekular yang berbeda serta menginduksi pola mediator sitokin pro dan antiinflamasi yang berhubungan dengan pola manifestasi patologi yang berbeda. Marka mikrosatelit pada studi ini mampu mengidentifikasi asal usul sumber infeksi, dan tingkat virulensi isolat yang sedang bersirkulasi. Surra berpotensi sebagai emerging zoonosis, terutama bagi peternak didaerah wabah dan endemis.

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ABSTRACT
Introduction: Trypanosoma evansi is an extracellular homoflagellate of protozoan blood causing Surra. The disease attacks all vertebrates and potentially as zoonosis. Virulence analysis of T. evansi is a fundamental knowledge to determine treatment strategies of Surra in both outbreak and endemic areas. The aims of this study was to determine virulence variation of T. evansi isolates collected from various regions in Indonesia and to obtained genetic markers as well as cytokine profile in mice. In addition, serological test was also carried out to farmers living in a Surra outbreak area Methods: Total of 32 isolates of T. evansi corfirmed with multiplex PCR (ITS-1; Te Ro Tat 1.2 VSG and ESAG6 / 7), were further tested with inoculation 104 parasite in DDY mice strain. The population genotype study of T. evansi was evaluated with 8 microsatellite markers (Tbb-1, Tbb-5, Tbb-9, Tbb-10-CA MORF2, M6C8-CA, MEST-19AT, MT3033-AT). Two different virulence isolates, high-Bang87 and low-PML287 was selected to cytokine profile analysis using ELISA, while farmers sera were tested using CATT and FELISA kits Results: A total of 32 local isolates of T. evansi tested were divided into three different virulences, i.e. 17 high virulence isolates, 11 moderate virulence and 4 low virulence isolates forming 8 pattern parasitemia levels. Based on Neigbour Joining (NJ) on 8 Microsatellite Multilocus Genotype (MLGs) was grouped into 4 populations (MLG A, MLG B, MLG C and MLG D). Stucture population analysis also provided the similar result generating 4 clusters. These results indicated that the markers used in this study had a specific location property. Three markers (TBB-1, and MEST M6C8-CA-19) showed an association between virulence and MLG. IFN-γ levels increased significantly in mice infected with Bang 87 isolate on 4th day post infection (dpi) having a significant negative correlation (p <0.05) with increased IL-10 levels, whereas in mice infected by PML 287 isolate, IFN-γ levels were positively correlated with IL- 10 levels. Early death in mice infected with Bang87 isolates was caused by systemic inflammatory response syndrome (SIRS). Result of serological test showed that 4 out of 24 farmers sera (16.67%) from outbreak areas are positive and all sample from free area are negative. Conclusion: Virulence variation of T. evansi isolates from Indonesia has different molecular character and induces cytokine pattern of pro and antiinflammatory mediators associated with distinct patterns of pathological manifestations. The microsatellite markers found in this study are able to identify origin of infection sources dan determine virulence of isolates that circulate on the outbreak area. Surra is potential new emerging disease, particularly for farmers or immunosurpressed individuals who living in both endemic and outbreak areas;Introduction: Trypanosoma evansi is an extracellular homoflagellate of protozoan blood causing Surra. The disease attacks all vertebrates and potentially as zoonosis. Virulence analysis of T. evansi is a fundamental knowledge to determine treatment strategies of Surra in both outbreak and endemic areas. The aims of this study was to determine virulence variation of T. evansi isolates collected from various regions in Indonesia and to obtained genetic markers as well as cytokine profile in mice. In addition, serological test was also carried out to farmers living in a Surra outbreak area Methods: Total of 32 isolates of T. evansi corfirmed with multiplex PCR (ITS-1; Te Ro Tat 1.2 VSG and ESAG6 / 7), were further tested with inoculation 104 parasite in DDY mice strain. The population genotype study of T. evansi was evaluated with 8 microsatellite markers (Tbb-1, Tbb-5, Tbb-9, Tbb-10-CA MORF2, M6C8-CA, MEST-19AT, MT3033-AT). Two different virulence isolates, high-Bang87 and low-PML287 was selected to cytokine profile analysis using ELISA, while farmers sera were tested using CATT and FELISA kits Results: A total of 32 local isolates of T. evansi tested were divided into three different virulences, i.e. 17 high virulence isolates, 11 moderate virulence and 4 low virulence isolates forming 8 pattern parasitemia levels. Based on Neigbour Joining (NJ) on 8 Microsatellite Multilocus Genotype (MLGs) was grouped into 4 populations (MLG A, MLG B, MLG C and MLG D). Stucture population analysis also provided the similar result generating 4 clusters. These results indicated that the markers used in this study had a specific location property. Three markers (TBB-1, and MEST M6C8-CA-19) showed an association between virulence and MLG. IFN-γ levels increased significantly in mice infected with Bang 87 isolate on 4th day post infection (dpi) having a significant negative correlation (p <0.05) with increased IL-10 levels, whereas in mice infected by PML 287 isolate, IFN-γ levels were positively correlated with IL- 10 levels. Early death in mice infected with Bang87 isolates was caused by systemic inflammatory response syndrome (SIRS). Result of serological test showed that 4 out of 24 farmers sera (16.67%) from outbreak areas are positive and all sample from free area are negative. Conclusion: Virulence variation of T. evansi isolates from Indonesia has different molecular character and induces cytokine pattern of pro and antiinflammatory mediators associated with distinct patterns of pathological manifestations. The microsatellite markers found in this study are able to identify origin of infection sources dan determine virulence of isolates that circulate on the outbreak area. Surra is potential new emerging disease, particularly for farmers or immunosurpressed individuals who living in both endemic and outbreak areas;Introduction: Trypanosoma evansi is an extracellular homoflagellate of protozoan blood causing Surra. The disease attacks all vertebrates and potentially as zoonosis. Virulence analysis of T. evansi is a fundamental knowledge to determine treatment strategies of Surra in both outbreak and endemic areas. The aims of this study was to determine virulence variation of T. evansi isolates collected from various regions in Indonesia and to obtained genetic markers as well as cytokine profile in mice. In addition, serological test was also carried out to farmers living in a Surra outbreak area Methods: Total of 32 isolates of T. evansi corfirmed with multiplex PCR (ITS-1; Te Ro Tat 1.2 VSG and ESAG6 / 7), were further tested with inoculation 104 parasite in DDY mice strain. The population genotype study of T. evansi was evaluated with 8 microsatellite markers (Tbb-1, Tbb-5, Tbb-9, Tbb-10-CA MORF2, M6C8-CA, MEST-19AT, MT3033-AT). Two different virulence isolates, high-Bang87 and low-PML287 was selected to cytokine profile analysis using ELISA, while farmers sera were tested using CATT and FELISA kits Results: A total of 32 local isolates of T. evansi tested were divided into three different virulences, i.e. 17 high virulence isolates, 11 moderate virulence and 4 low virulence isolates forming 8 pattern parasitemia levels. Based on Neigbour Joining (NJ) on 8 Microsatellite Multilocus Genotype (MLGs) was grouped into 4 populations (MLG A, MLG B, MLG C and MLG D). Stucture population analysis also provided the similar result generating 4 clusters. These results indicated that the markers used in this study had a specific location property. Three markers (TBB-1, and MEST M6C8-CA-19) showed an association between virulence and MLG. IFN-γ levels increased significantly in mice infected with Bang 87 isolate on 4th day post infection (dpi) having a significant negative correlation (p <0.05) with increased IL-10 levels, whereas in mice infected by PML 287 isolate, IFN-γ levels were positively correlated with IL- 10 levels. Early death in mice infected with Bang87 isolates was caused by systemic inflammatory response syndrome (SIRS). Result of serological test showed that 4 out of 24 farmers sera (16.67%) from outbreak areas are positive and all sample from free area are negative. Conclusion: Virulence variation of T. evansi isolates from Indonesia has different molecular character and induces cytokine pattern of pro and antiinflammatory mediators associated with distinct patterns of pathological manifestations. The microsatellite markers found in this study are able to identify origin of infection sources dan determine virulence of isolates that circulate on the outbreak area. Surra is potential new emerging disease, particularly for farmers or immunosurpressed individuals who living in both endemic and outbreak areas;Introduction: Trypanosoma evansi is an extracellular homoflagellate of protozoan blood causing Surra. The disease attacks all vertebrates and potentially as zoonosis. Virulence analysis of T. evansi is a fundamental knowledge to determine treatment strategies of Surra in both outbreak and endemic areas. The aims of this study was to determine virulence variation of T. evansi isolates collected from various regions in Indonesia and to obtained genetic markers as well as cytokine profile in mice. In addition, serological test was also carried out to farmers living in a Surra outbreak area Methods: Total of 32 isolates of T. evansi corfirmed with multiplex PCR (ITS-1; Te Ro Tat 1.2 VSG and ESAG6 / 7), were further tested with inoculation 104 parasite in DDY mice strain. The population genotype study of T. evansi was evaluated with 8 microsatellite markers (Tbb-1, Tbb-5, Tbb-9, Tbb-10-CA MORF2, M6C8-CA, MEST-19AT, MT3033-AT). Two different virulence isolates, high-Bang87 and low-PML287 was selected to cytokine profile analysis using ELISA, while farmers sera were tested using CATT and FELISA kits Results: A total of 32 local isolates of T. evansi tested were divided into three different virulences, i.e. 17 high virulence isolates, 11 moderate virulence and 4 low virulence isolates forming 8 pattern parasitemia levels. Based on Neigbour Joining (NJ) on 8 Microsatellite Multilocus Genotype (MLGs) was grouped into 4 populations (MLG A, MLG B, MLG C and MLG D). Stucture population analysis also provided the similar result generating 4 clusters. These results indicated that the markers used in this study had a specific location property. Three markers (TBB-1, and MEST M6C8-CA-19) showed an association between virulence and MLG. IFN-γ levels increased significantly in mice infected with Bang 87 isolate on 4th day post infection (dpi) having a significant negative correlation (p <0.05) with increased IL-10 levels, whereas in mice infected by PML 287 isolate, IFN-γ levels were positively correlated with IL- 10 levels. Early death in mice infected with Bang87 isolates was caused by systemic inflammatory response syndrome (SIRS). Result of serological test showed that 4 out of 24 farmers sera (16.67%) from outbreak areas are positive and all sample from free area are negative. Conclusion: Virulence variation of T. evansi isolates from Indonesia has different molecular character and induces cytokine pattern of pro and antiinflammatory mediators associated with distinct patterns of pathological manifestations. The microsatellite markers found in this study are able to identify origin of infection sources dan determine virulence of isolates that circulate on the outbreak area. Surra is potential new emerging disease, particularly for farmers or immunosurpressed individuals who living in both endemic and outbreak areas;Introduction: Trypanosoma evansi is an extracellular homoflagellate of protozoan blood causing Surra. The disease attacks all vertebrates and potentially as zoonosis. Virulence analysis of T. evansi is a fundamental knowledge to determine treatment strategies of Surra in both outbreak and endemic areas. The aims of this study was to determine virulence variation of T. evansi isolates collected from various regions in Indonesia and to obtained genetic markers as well as cytokine profile in mice. In addition, serological test was also carried out to farmers living in a Surra outbreak area Methods: Total of 32 isolates of T. evansi corfirmed with multiplex PCR (ITS-1; Te Ro Tat 1.2 VSG and ESAG6 / 7), were further tested with inoculation 104 parasite in DDY mice strain. The population genotype study of T. evansi was evaluated with 8 microsatellite markers (Tbb-1, Tbb-5, Tbb-9, Tbb-10-CA MORF2, M6C8-CA, MEST-19AT, MT3033-AT). Two different virulence isolates, high-Bang87 and low-PML287 was selected to cytokine profile analysis using ELISA, while farmers sera were tested using CATT and FELISA kits Results: A total of 32 local isolates of T. evansi tested were divided into three different virulences, i.e. 17 high virulence isolates, 11 moderate virulence and 4 low virulence isolates forming 8 pattern parasitemia levels. Based on Neigbour Joining (NJ) on 8 Microsatellite Multilocus Genotype (MLGs) was grouped into 4 populations (MLG A, MLG B, MLG C and MLG D). Stucture population analysis also provided the similar result generating 4 clusters. These results indicated that the markers used in this study had a specific location property. Three markers (TBB-1, and MEST M6C8-CA-19) showed an association between virulence and MLG. IFN-γ levels increased significantly in mice infected with Bang 87 isolate on 4th day post infection (dpi) having a significant negative correlation (p <0.05) with increased IL-10 levels, whereas in mice infected by PML 287 isolate, IFN-γ levels were positively correlated with IL- 10 levels. Early death in mice infected with Bang87 isolates was caused by systemic inflammatory response syndrome (SIRS). Result of serological test showed that 4 out of 24 farmers sera (16.67%) from outbreak areas are positive and all sample from free area are negative. Conclusion: Virulence variation of T. evansi isolates from Indonesia has different molecular character and induces cytokine pattern of pro and antiinflammatory mediators associated with distinct patterns of pathological manifestations. The microsatellite markers found in this study are able to identify origin of infection sources dan determine virulence of isolates that circulate on the outbreak area. Surra is potential new emerging disease, particularly for farmers or immunosurpressed individuals who living in both endemic and outbreak areas;Introduction: Trypanosoma evansi is an extracellular homoflagellate of protozoan blood causing Surra. The disease attacks all vertebrates and potentially as zoonosis. Virulence analysis of T. evansi is a fundamental knowledge to determine treatment strategies of Surra in both outbreak and endemic areas. The aims of this study was to determine virulence variation of T. evansi isolates collected from various regions in Indonesia and to obtained genetic markers as well as cytokine profile in mice. In addition, serological test was also carried out to farmers living in a Surra outbreak area Methods: Total of 32 isolates of T. evansi corfirmed with multiplex PCR (ITS-1; Te Ro Tat 1.2 VSG and ESAG6 / 7), were further tested with inoculation 104 parasite in DDY mice strain. The population genotype study of T. evansi was evaluated with 8 microsatellite markers (Tbb-1, Tbb-5, Tbb-9, Tbb-10-CA MORF2, M6C8-CA, MEST-19AT, MT3033-AT). Two different virulence isolates, high-Bang87 and low-PML287 was selected to cytokine profile analysis using ELISA, while farmers sera were tested using CATT and FELISA kits Results: A total of 32 local isolates of T. evansi tested were divided into three different virulences, i.e. 17 high virulence isolates, 11 moderate virulence and 4 low virulence isolates forming 8 pattern parasitemia levels. Based on Neigbour Joining (NJ) on 8 Microsatellite Multilocus Genotype (MLGs) was grouped into 4 populations (MLG A, MLG B, MLG C and MLG D). Stucture population analysis also provided the similar result generating 4 clusters. These results indicated that the markers used in this study had a specific location property. Three markers (TBB-1, and MEST M6C8-CA-19) showed an association between virulence and MLG. IFN-γ levels increased significantly in mice infected with Bang 87 isolate on 4th day post infection (dpi) having a significant negative correlation (p <0.05) with increased IL-10 levels, whereas in mice infected by PML 287 isolate, IFN-γ levels were positively correlated with IL- 10 levels. Early death in mice infected with Bang87 isolates was caused by systemic inflammatory response syndrome (SIRS). Result of serological test showed that 4 out of 24 farmers sera (16.67%) from outbreak areas are positive and all sample from free area are negative. Conclusion: Virulence variation of T. evansi isolates from Indonesia has different molecular character and induces cytokine pattern of pro and antiinflammatory mediators associated with distinct patterns of pathological manifestations. The microsatellite markers found in this study are able to identify origin of infection sources dan determine virulence of isolates that circulate on the outbreak area. Surra is potential new emerging disease, particularly for farmers or immunosurpressed individuals who living in both endemic and outbreak areas;Introduction: Trypanosoma evansi is an extracellular homoflagellate of protozoan blood causing Surra. The disease attacks all vertebrates and potentially as zoonosis. Virulence analysis of T. evansi is a fundamental knowledge to determine treatment strategies of Surra in both outbreak and endemic areas. The aims of this study was to determine virulence variation of T. evansi isolates collected from various regions in Indonesia and to obtained genetic markers as well as cytokine profile in mice. In addition, serological test was also carried out to farmers living in a Surra outbreak area Methods: Total of 32 isolates of T. evansi corfirmed with multiplex PCR (ITS-1; Te Ro Tat 1.2 VSG and ESAG6 / 7), were further tested with inoculation 104 parasite in DDY mice strain. The population genotype study of T. evansi was evaluated with 8 microsatellite markers (Tbb-1, Tbb-5, Tbb-9, Tbb-10-CA MORF2, M6C8-CA, MEST-19AT, MT3033-AT). Two different virulence isolates, high-Bang87 and low-PML287 was selected to cytokine profile analysis using ELISA, while farmers sera were tested using CATT and FELISA kits Results: A total of 32 local isolates of T. evansi tested were divided into three different virulences, i.e. 17 high virulence isolates, 11 moderate virulence and 4 low virulence isolates forming 8 pattern parasitemia levels. Based on Neigbour Joining (NJ) on 8 Microsatellite Multilocus Genotype (MLGs) was grouped into 4 populations (MLG A, MLG B, MLG C and MLG D). Stucture population analysis also provided the similar result generating 4 clusters. These results indicated that the markers used in this study had a specific location property. Three markers (TBB-1, and MEST M6C8-CA-19) showed an association between virulence and MLG. IFN-γ levels increased significantly in mice infected with Bang 87 isolate on 4th day post infection (dpi) having a significant negative correlation (p <0.05) with increased IL-10 levels, whereas in mice infected by PML 287 isolate, IFN-γ levels were positively correlated with IL- 10 levels. Early death in mice infected with Bang87 isolates was caused by systemic inflammatory response syndrome (SIRS). Result of serological test showed that 4 out of 24 farmers sera (16.67%) from outbreak areas are positive and all sample from free area are negative. Conclusion: Virulence variation of T. evansi isolates from Indonesia has different molecular character and induces cytokine pattern of pro and antiinflammatory mediators associated with distinct patterns of pathological manifestations. The microsatellite markers found in this study are able to identify origin of infection sources dan determine virulence of isolates that circulate on the outbreak area. Surra is potential new emerging disease, particularly for farmers or immunosurpressed individuals who living in both endemic and outbreak areas;Introduction: Trypanosoma evansi is an extracellular homoflagellate of protozoan blood causing Surra. The disease attacks all vertebrates and potentially as zoonosis. Virulence analysis of T. evansi is a fundamental knowledge to determine treatment strategies of Surra in both outbreak and endemic areas. The aims of this study was to determine virulence variation of T. evansi isolates collected from various regions in Indonesia and to obtained genetic markers as well as cytokine profile in mice. In addition, serological test was also carried out to farmers living in a Surra outbreak area Methods: Total of 32 isolates of T. evansi corfirmed with multiplex PCR (ITS-1; Te Ro Tat 1.2 VSG and ESAG6 / 7), were further tested with inoculation 104 parasite in DDY mice strain. The population genotype study of T. evansi was evaluated with 8 microsatellite markers (Tbb-1, Tbb-5, Tbb-9, Tbb-10-CA MORF2, M6C8-CA, MEST-19AT, MT3033-AT). Two different virulence isolates, high-Bang87 and low-PML287 was selected to cytokine profile analysis using ELISA, while farmers sera were tested using CATT and FELISA kits Results: A total of 32 local isolates of T. evansi tested were divided into three different virulences, i.e. 17 high virulence isolates, 11 moderate virulence and 4 low virulence isolates forming 8 pattern parasitemia levels. Based on Neigbour Joining (NJ) on 8 Microsatellite Multilocus Genotype (MLGs) was grouped into 4 populations (MLG A, MLG B, MLG C and MLG D). Stucture population analysis also provided the similar result generating 4 clusters. These results indicated that the markers used in this study had a specific location property. Three markers (TBB-1, and MEST M6C8-CA-19) showed an association between virulence and MLG. IFN-γ levels increased significantly in mice infected with Bang 87 isolate on 4th day post infection (dpi) having a significant negative correlation (p <0.05) with increased IL-10 levels, whereas in mice infected by PML 287 isolate, IFN-γ levels were positively correlated with IL- 10 levels. Early death in mice infected with Bang87 isolates was caused by systemic inflammatory response syndrome (SIRS). Result of serological test showed that 4 out of 24 farmers sera (16.67%) from outbreak areas are positive and all sample from free area are negative. Conclusion: Virulence variation of T. evansi isolates from Indonesia has different molecular character and induces cytokine pattern of pro and antiinflammatory mediators associated with distinct patterns of pathological manifestations. The microsatellite markers found in this study are able to identify origin of infection sources dan determine virulence of isolates that circulate on the outbreak area. Surra is potential new emerging disease, particularly for farmers or immunosurpressed individuals who living in both endemic and outbreak areas;Introduction: Trypanosoma evansi is an extracellular homoflagellate of protozoan blood causing Surra. The disease attacks all vertebrates and potentially as zoonosis. Virulence analysis of T. evansi is a fundamental knowledge to determine treatment strategies of Surra in both outbreak and endemic areas. The aims of this study was to determine virulence variation of T. evansi isolates collected from various regions in Indonesia and to obtained genetic markers as well as cytokine profile in mice. In addition, serological test was also carried out to farmers living in a Surra outbreak area Methods: Total of 32 isolates of T. evansi corfirmed with multiplex PCR (ITS-1; Te Ro Tat 1.2 VSG and ESAG6 / 7), were further tested with inoculation 104 parasite in DDY mice strain. The population genotype study of T. evansi was evaluated with 8 microsatellite markers (Tbb-1, Tbb-5, Tbb-9, Tbb-10-CA MORF2, M6C8-CA, MEST-19AT, MT3033-AT). Two different virulence isolates, high-Bang87 and low-PML287 was selected to cytokine profile analysis using ELISA, while farmers sera were tested using CATT and FELISA kits Results: A total of 32 local isolates of T. evansi tested were divided into three different virulences, i.e. 17 high virulence isolates, 11 moderate virulence and 4 low virulence isolates forming 8 pattern parasitemia levels. Based on Neigbour Joining (NJ) on 8 Microsatellite Multilocus Genotype (MLGs) was grouped into 4 populations (MLG A, MLG B, MLG C and MLG D). Stucture population analysis also provided the similar result generating 4 clusters. These results indicated that the markers used in this study had a specific location property. Three markers (TBB-1, and MEST M6C8-CA-19) showed an association between virulence and MLG. IFN-γ levels increased significantly in mice infected with Bang 87 isolate on 4th day post infection (dpi) having a significant negative correlation (p <0.05) with increased IL-10 levels, whereas in mice infected by PML 287 isolate, IFN-γ levels were positively correlated with IL- 10 levels. Early death in mice infected with Bang87 isolates was caused by systemic inflammatory response syndrome (SIRS). Result of serological test showed that 4 out of 24 farmers sera (16.67%) from outbreak areas are positive and all sample from free area are negative. Conclusion: Virulence variation of T. evansi isolates from Indonesia has different molecular character and induces cytokine pattern of pro and antiinflammatory mediators associated with distinct patterns of pathological manifestations. The microsatellite markers found in this study are able to identify origin of infection sources dan determine virulence of isolates that circulate on the outbreak area. Surra is potential new emerging disease, particularly for farmers or immunosurpressed individuals who living in both endemic and outbreak areas

Abstrak :
Introduction: Constant exposure to a variety of microorganisms in domestic environment plays an important role in the shaping of individual immune response mechanism, which can affect one's susceptibility to the diseases. The aim of the study to get an understanding how the exposure of microorganisms in the the different area where the people living might give a contribution to the profile and the regulation of the immune respons after stimulated to malaria, vaccine BCG and oxLDL antigents in PBMC and whole blood cultures, and to evaluate the character of T reg as a mediator to suppress the cell proliferation. Methode: It is an in vitro experimental study performed at Laboratorium Terpadu, Faculty of Medicine Univertas Indonesia, Jakarta in 2013 2014. As a model of infectious diseases is used pathogenic antigents such as Plasmodium falciparum infected red blood cells malaria and bacille calmette gu rin BCG vaccine, and as a modell of inflammatory disease is used non a patonegic antigen, low density lipoprotein LDL . Whole blood cultures is done for 80 blood samples to know how the regulation of immune respons from people living a rural populatin. PBMC cultures is also done to explore macrophages after stimulated to malaria, BCG and LDL. PHA stimulated to the PBMC culture with and without T reg cells to evaluate the character of T reg. T regulatory cells perhaps play the important roles to suppress the immune respons to microorganisms was also done. Results: The profile of the immune respons of the people living in the unslum area is significantly more inflamatif than that in the slum area. The ratio of pro anti inflammation cytokines TNF IL 10 of the people living in the unslum area is significantly higher than that in the slum area. This is marked by increasing of oxLDL accumulationis that is the important point of the low protection to oxLDL of the people living in the unslum area p 0.01 . T regulatory cell may suppress the proliferation in the PBMC culture for the people living in the slum area marked by increasing not only the expression of IL 10 cytokines but also the sum of T regulatory sells p 0.01 significantly. Conclusion: The immune respons of the people living in the unslum area is more inflamatif and responsive to malaria, BCG vaccine and oxLDL. The character of macrophage of the people living in the slum area is marked by the low ratio of pro anti inflammation cytokines TNF IL 10 to malaria, BCG vaccine and oxLDLstimulations. T regulatory cell may suppress the proliferation in the PBMC culture for the people living in the slum.

Abstrak :
Pendahuluan: Interaksi Cryptococcus neoformans dengan makrofag mempengaruhi kejadian kriptokokosis meningeal, infeksi oportunistik fatal pada populasi AIDS, dimana pada keadaan imunokompromi, kemampuan fagositosis makrofag terganggu. Penelitian ini bertujuan untuk menganalisis aktifitas fagositik makrofag penderita HIV, profil sitokin yang terbentuk serta pengaruh pemberian obat anti retroviral. Metode: Desain penelitian eksploratif-analitik terhadap interaksi makrofag-C. neoformans. Makrofag pasien HIV dan orang sehat (selanjutnya disebut Kasus dan Kontrol). Penelitian mencakup pengukuran kadar nitrit petanda aktivasi makrofag, uji indeks internalisasi jamur (IIJ), laju fagositosis (LF), dan daya bunuh (DB) makrofag terhadap jamur yang diamati pada menit ke 30, 120 dan 240. Selain itu juga diteliti profil sitokin yang terbentuk (IL-5, IL-10, IL-6, TNF-?, IFN-?) dan uji serologis terhadap plasma menggunakan Cryptococcus antigen lateral flow assay (CrAg-LFA). Hasil: Terkumpul 38 Kasus dan 42 Kontrol dengan hasil uji LFA seluruh subyek, Kasus maupun Kontrol, negatif. Kadar nitrit yang terbentuk lebih tinggi pada kelompok Kontrol. IIJ makrofag Kasus lebih tinggi pada T30 dan T120. LF makrofag kontrol lebih tinggi pada T30 dan T120. DB makrofag Kontrol jauh lebih tinggi dibanding makrofag Kasus pada seluruh pengamatan. Pola sitokin yang terbentuk oleh makrofag kasus mengarah ke sitokin anti inflamasi (IL-5 dan IL-10 tinggi), sedangkan pola sitokin yng terbentuk oleh makrofag Kontrol mengarah ke sitokin pro inflamasi (IL-6 dan IFN-? tinggi) kecuali untuk TNF-? yang lebih tinggi pada supernatan makrofag Kasus. Pembahasan: Aktifitas fagositik makrofag Kasus terganggu, ditandai dengan daya bunuh yang jauh lebih rendah. Selain itu, tingginya kadar sitokin pro inflamasi pada populasi kontrol menunjukkan pembersihan jamur yang lebih efektif sedangkan sitokin anti-inflamasi yang lebih tinggi pada subjek terinfeksi HIV memungkinkan terjadinya parasitisme intraseluler makrofag oleh C. neoformans. Kesimpulan: terdapat perbedaan daya bunuh dan pola sitokin pro dan anti inflamasi pada subjek terinfeksi HIV dibanding kontrol. ......Introduction: interaction of Cryptococcus neoformans-macrophage affecting the incidence of cryptococcal meningitis, a fatal opportunistic infection in AIDS population. In immunocompromised condition, macrophage phagocytic activity was impaired. This study aimed to analyze phagocytic activity of macrophage derived from HIV infected individuals against C. neoformans, the cytokine profile and the role of antiretroviral therapy in that interaction. Method: using explorative-analytical design on the interaction between macrophageyeast seen as: internalization index, phagocytic rate, killing ability, production of cytokine and NO. We also tested the plasma against Cryptococcus antigen lateral flow assay (CrAg-LFA). Result: out of 38 HIV(+) subjects and 42 healthy subject all were negatif for LFA. Nitrite formed were higher in the Control group. Internalization index were higher in the Cases group, Phagocytosis rate were higher in the Control group: Killing ability were far superior in the Control group. Cytokine profile of the Cases group were anti inflammatory (higher IL-5 and IL-10) while in the Control group, were more pro inflammatory (higher IL-6 and IFN-?) with the exception of TNF-? which was higher in the Cases group. Discussion: the higher level of pro-inflammatory cytokine among control group represent a more effective clearance of fungal by macrophages while higher level of anti-inflamatory cytokine among HIV+vderived macrophage indicates profound intracellular parasitism of macrophage by C. neoformans. Conclusion: there is difference of killing ability, NO production and antiinflammatory cytokine production among macrophage derived from healthy subjects that showed us a more effective fungal clearance and activation of macrophage.

Abstrak :
Latar Belakang: Spatially Fractionated Grid Radiotherapy (SFGRT) dilaporkan berperan dalam tatalaksana tumor berukuran besar, termasuk karsinoma sel hati (KSH). Namun, pengetahuan mekanisme kerja SFGRT masih terbatas. Studi hewan coba besar dapat bermanfaat untuk menambah bukti ilmiah, dimana studi ini merupakan studi pertama induksi KSH dengan N-Diethylnitrosamine (DENA) pada babi domestik. Penelitian ini bertujuan untuk mengevaluasi pola kematian sel, efek bystander, efek abscopal, serta respons imun dari SFGRT pada hewan coba besar dengan KSH. Metode: Uji eksperimental dilakukan pada 10 babi domestik (Sus scrofa domesticus) yang diinduksi dengan injeksi DENA 15 mg/kgBB dan fenobarbital (PB) 4 mg/kgBB. Subjek dievaluasi secara periodik menggunakan USG, CT scan, analisa darah. Diagnosis KSH ditegakkan dengan pemeriksaan imaging dan histopatologi. Subjek dirandomisasi sebagai kontrol negatif, kontrol positif, penerima intervensi SFGRT1x20 Gy dosis tunggal, atau penerima intervensi radiasi lengkap SFGRT 1x20 Gy + Stereotactic Body Radiotherapy (SBRT) 3x8 Gy. Pemeriksaan flowcytometryAnnexin dilakukan untuk melihat pola kematian sel, dan biomarker TNF-a, IFN-ɣ, FOXP3 untuk melihat respons jaringan tumor dan jaringan hati di dalam dan di luararea radiasi. Hasil: Karsinogenesis berhasil pada seluruh subjek setelah 15-22 bulan induksi, berupa KSH dan angiosarkoma hepatik. Peningkatan FOXP3 diamati pada subjek yang mengalami keganasan dibandingkan kontrol negatif, sementara TNF-a dan IFN-ɣ mengalami penurunan. Pemeriksaan Annexin menunjukkan rendahnya jumlah sel viabel signifikan pada perlakuan radiasi lengkap SFGRT+SBRT (18.65%) dibandingkan grup SFGRT saja (63,13%-89,09%). Sel viabel tumor di luar area radiasi juga terdapat penurunan, menunjukkan kemungkinan efek bystander. EkspresiFOXP3 mengalami penurunan dan terjadi peningkatan %CD8+ pasca perlakuanradiasi. Kesimpulan: Induksi KSH pada babi domestik dapat dilakukan dengan pemberian DENA+PB dengan periode latensi 15-22 bulan. Penurunan jumlah sel viabel secara signifikan tampak pada kelompok perlakuan radiasi lengkap (SFGRT 1x20Gy + SBRT 3x8Gy) dengan jalur apoptosis pada area di dalam dan di luar area radiasi yang menunjukkan peran efek bystander/abscopal.

Abstrak :
[ABSTRAK
Pendahuluan: Di Indonesia belum ada penelitian tentang injeksi silikon dan komplikasinya, walaupun kasusnya banyak. Patogenesis granuloma silikon masih belum jelas. Beberapa penelitian mengemukakan peran sel T dan sitokin, namun belum ada yang meneliti tentang toleransi imun. Metode: Penelitian ini merupakan penelitian deskriptif analitik meliputi rancangan potong lintang membandingkan 3 kelompok, yaitu 31 jaringan granuloma dan 31 kulit submental pasien dengan suntikan silikon di dagu (kasus) dan 37 kulit normal (kontrol), terhadap gambaran klinis, histopatologis, dan respons imun melalui ekspresi sitokin TNF-a, IFN-g, IL-10, enzim IDO, serta sel Treg (CD4+CD25+); Penelitian eksperimental membiakkan darah penuh kasus dan orang normal, pada RPMI, dan RPMI yang distimulasi PHA, dan silikon. Dilanjutkan dengan mengukur kadar sitokin TNF-a, IFN-g, IL-10 dan IDO supernatan biakan darah. Penelitian dilakukan di klinik spesialis JMB, FMIPA, FKUI, FKUNAIR, dan lembaga Eijkman, tahun 2012 - 2014. Hasil Penelitian: Sebanyak 31 pasien granuloma akibat suntikan silikon di dagu umumnya datang berobat 12,5 tahun setelah penyuntikan, perubahan bentuk dagu terjadi pada tahun ke-4, perubahan warna pada tahun ke-5. Kadar sitokin proinflamasi di supernatan biakan darah lebih tinggi pada pasien granuloma daripada normal. Terdapat korelasi bermakna antara TNF-a di supernatan biakan darah dengan ekspresi TNF-a di jaringan granuloma. Enzim IDO, Treg, IL-10 di kulit submental berkorelasi bermakna dengan sitokin di granuloma. Sitokin anti inflamasi berperan pada kulit submental. Rasio TNF-a/IL-10 di supernatan biakan darah berkorelasi terbalik dengan ekspresi sel Treg di granuloma, membuktikan fungsi Treg sebagai toleransi imun, bekerja melalui IL-10. Enzim IDO di granuloma berkolerasi bermakna dengan rasio TNF-a/IL-10 di supernatan biakan darah dan Treg kulit submental. Simpulan: Enzim IDO bekerja sama dengan fungsi sel Treg dalam toleransi imun pada granuloma akibat suntikan silikon. TNF-a di supernatan biakan darah dan sitokin anti inflamasi di kulit submental dapat dijadikan prediktor untuk menilai respons imun yang terjadi akibat suntikan silikon.;

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ABSTRACT
Background: There is no study on silicone injections and its complications in Indonesia, yet, although the number of cases increased. The pathogenesis of silicone granulomas is still unclear. A few studies have been made to investigate the role of T cells and cytokines, however, none investigates the role of immune tolerance. Method: An analytical descriptive study encompassing cross sectional research was designed to compare 3 groups of 31 granuloma tissue and 31 submental skin of the patients with silicone injection in the chin (case) and 37 normal skin (control) on the clinical pictures, histopathological features and immune response through the expression of TNF-a, IFN-g, IL-10 cytokines, IDO enzyme, and Treg cells (CD4+CD25+). The experimental study cultured whole blood of the case and control patients and measured the level of TNF-a, IFN-g, IL-10 cytokines and IDO enzyme. The study was conducted in JMB specialist clinics, FMIPA, FKUI, FKUA, and Eijkman foundation from the year 2012 to 2014. Result: Thirty one patients with granuloma caused by silicone injection in the chin commonly seek medical advice 12.5 years after the injection, the chin shape changed on the fourth year and the skin color changed on the fifth year. Patients with granuloma had higher level of proinflammatory cytokines in their blood cultured supernatant. There was a significant correlation between TNF-a in blood cultured supernatant with the expression of TNF-a in the granuloma tissue. IDO enzyme, Treg cells, IL-10 in the submental skin significantly correlated with the cytokines in the granulomas. Anti inflammatory cytokines played a role on the submental skin. The ratio of TNF-a/IL-10 in blood cultured supernatant reversely correlated with the expression of Treg cells in the granuloma, demonstrating the function of Treg cells as an immune tolerance working through IL-10. IDO enzyme in the granulomas significantly correlated with the ratio of TNF-a/IL-10 in blood cultured supernatant and Treg in the submental skin. Conclusion: IDO enzyme collaborates with Treg cells in the immune tolerance caused by silicone injection. TNF-a in blood cultured supernatant and anti inflammatory cytokines in the submental skin can be utilized as predictors to assess the resulting immune response due to silicone injection. ;Background: There is no study on silicone injections and its complications in Indonesia, yet, although the number of cases increased. The pathogenesis of silicone granulomas is still unclear. A few studies have been made to investigate the role of T cells and cytokines, however, none investigates the role of immune tolerance. Method: An analytical descriptive study encompassing cross sectional research was designed to compare 3 groups of 31 granuloma tissue and 31 submental skin of the patients with silicone injection in the chin (case) and 37 normal skin (control) on the clinical pictures, histopathological features and immune response through the expression of TNF-a, IFN-g, IL-10 cytokines, IDO enzyme, and Treg cells (CD4+CD25+). The experimental study cultured whole blood of the case and control patients and measured the level of TNF-a, IFN-g, IL-10 cytokines and IDO enzyme. The study was conducted in JMB specialist clinics, FMIPA, FKUI, FKUA, and Eijkman foundation from the year 2012 to 2014. Result: Thirty one patients with granuloma caused by silicone injection in the chin commonly seek medical advice 12.5 years after the injection, the chin shape changed on the fourth year and the skin color changed on the fifth year. Patients with granuloma had higher level of proinflammatory cytokines in their blood cultured supernatant. There was a significant correlation between TNF-a in blood cultured supernatant with the expression of TNF-a in the granuloma tissue. IDO enzyme, Treg cells, IL-10 in the submental skin significantly correlated with the cytokines in the granulomas. Anti inflammatory cytokines played a role on the submental skin. The ratio of TNF-a/IL-10 in blood cultured supernatant reversely correlated with the expression of Treg cells in the granuloma, demonstrating the function of Treg cells as an immune tolerance working through IL-10. IDO enzyme in the granulomas significantly correlated with the ratio of TNF-a/IL-10 in blood cultured supernatant and Treg in the submental skin. Conclusion: IDO enzyme collaborates with Treg cells in the immune tolerance caused by silicone injection. TNF-a in blood cultured supernatant and anti inflammatory cytokines in the submental skin can be utilized as predictors to assess the resulting immune response due to silicone injection. , Background: There is no study on silicone injections and its complications in Indonesia, yet, although the number of cases increased. The pathogenesis of silicone granulomas is still unclear. A few studies have been made to investigate the role of T cells and cytokines, however, none investigates the role of immune tolerance. Method: An analytical descriptive study encompassing cross sectional research was designed to compare 3 groups of 31 granuloma tissue and 31 submental skin of the patients with silicone injection in the chin (case) and 37 normal skin (control) on the clinical pictures, histopathological features and immune response through the expression of TNF-a, IFN-g, IL-10 cytokines, IDO enzyme, and Treg cells (CD4+CD25+). The experimental study cultured whole blood of the case and control patients and measured the level of TNF-a, IFN-g, IL-10 cytokines and IDO enzyme. The study was conducted in JMB specialist clinics, FMIPA, FKUI, FKUA, and Eijkman foundation from the year 2012 to 2014. Result: Thirty one patients with granuloma caused by silicone injection in the chin commonly seek medical advice 12.5 years after the injection, the chin shape changed on the fourth year and the skin color changed on the fifth year. Patients with granuloma had higher level of proinflammatory cytokines in their blood cultured supernatant. There was a significant correlation between TNF-a in blood cultured supernatant with the expression of TNF-a in the granuloma tissue. IDO enzyme, Treg cells, IL-10 in the submental skin significantly correlated with the cytokines in the granulomas. Anti inflammatory cytokines played a role on the submental skin. The ratio of TNF-a/IL-10 in blood cultured supernatant reversely correlated with the expression of Treg cells in the granuloma, demonstrating the function of Treg cells as an immune tolerance working through IL-10. IDO enzyme in the granulomas significantly correlated with the ratio of TNF-a/IL-10 in blood cultured supernatant and Treg in the submental skin. Conclusion: IDO enzyme collaborates with Treg cells in the immune tolerance caused by silicone injection. TNF-a in blood cultured supernatant and anti inflammatory cytokines in the submental skin can be utilized as predictors to assess the resulting immune response due to silicone injection. ]