Suyanto Hadi
Fakultas Kedokteran Universitas Diponegoro

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Ekstrak Herbal (Daun Salam, Jintan Hitam, Daun Seledri) dan Kadar IL-6 Plasma Penderita Hiperurisemia Ngestiningsih, Dwi; Hadi, Suyanto
MEDIA MEDIKA INDONESIANA 2011:MMI Volume 45 Issue 2 Year 2011
Publisher : MEDIA MEDIKA INDONESIANA

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ABSTRACTHerbal extract (Eugenia polyantha, Nigella sativa, Apium graveolens) and IL-6 plasma level of hyperuricaemic patientsBackground: Hyperuricaemia stimulates pro-inflammatory cytokines like TNF-α, IL-1 and IL-6. They also will stimulate leucocyte adhesion molecule. Suplementation of bay-leaf (Eugenia polyantha), celery herb (Apium graveolens) and blackseed (Nigella sativa) had known to decrease inflammatory cytokines response including IL-6 blood level. These herbal are common in Indonesia but have not clinically studied correlation with IL-6 pro inflammatory cytokine in human. The aim study was to determine the effect of herbal extract on IL-6 blood level of hyperuricaemic patients.Methods: This study was an experimental study with double blind randomised clinical trial, held on 2007 March–2008 February. Samples were hyperuricaemic patiens in clinic and wards of internal medicine and geriatric RSUP Dr. Kariadi Semarang. They were divided into 2 groups: (1) Extract herbal and (2) placebo group. IL-6 blood level were tested before and 4 weeks after treatment using ELISA methode.Results: Subjects were 43 hyperuricaemic patients (22 in herbal treatment group compare with 21 in placebo group). The mean of basic IL-6 level in herbal group was 214.58 pg/dl whereas in placebo was 182.89 pg/dl. The mean of outcome IL-6 level in herbal group was 192.15 pg/dl whereas in placebo group was 254,00 pg/dl. The mean of IL-6 delta level in herbal group was -22.43 pg/dl whereas in placebo was 71.11 pg/dl (p:0.045). The mean of IL-6 ratio in herbal group was 1142.16% whereas in placebo was 754.45% (p:0.052).Conclusion: The herbal extract being used uric acid lowering agent decreases IL-6 level.Keywords: IL-6, Eugenia polyantha, Apium graveolens, Nigella sativaABSTRAKLatar belakang: Hiperurisemia akan memacu produksi sitokin proinflamasi TNF-α, IL-1 dan IL-6. Ketiga sitokin tadi akan memacu penarikan lekosit ke daerah deposit kristal monosodium urat dan melipatgandakan respon inflamasi. Daun salam (Eugenia polyantha), seledri (Apium graveolens), dan biji jinten hitam (Nigella sativa) pada percobaan terdahulu dapat menurunkan respon inflamasi termasuk kadar IL-6 pada respon inflamasi. Ketiga tanaman ini sangat banyak digunakan di Indonesia namun sampai saat ini belum dilakukan uji klinik pada manusia. Tujuan penelitian ini untuk mengetahui efek pemberian formula ekstrak herbal terhadap kadar IL-6 serum penderita hiperurisemia.Metoda: Penelitian ini adalah eksperimental yaitu double blind randomised clinical trial (RCT), dilaksanakan Maret 2007–Februari 2008. Subyek penelitian adalah penderita hiperurisemia usia 18 tahun yang berobat di Poliklinik/Rawat Inap Penyakit Dalam dan Geriatri RSUP Dr. Kariadi Semarang. Sampel dibagi menjadi kelompok perlakuan dan kelompok kelola. Dilakukan pemeriksaan kadar IL-6 darah sebelum dan setelah 4 minggu perlakuan. IL-6 diperiksa dengan cara ELISA.Hasil: Sampel sebanyak 43 orang (22 orang kelompok herbal dan 21 orang kelompok plasebo). Rerata kadar IL-6 awal kelompok herbal 214,58 pg/dl sedangkan kelompok plasebo 182,89 pg/dl. Rerata kadar IL-6 akhir kelompok herbal 192,15 pg/dl sedangkan kelompok plasebo 254,00 pg/dl. Rerata delta kadar IL-6 kelompok ekstrak herbal -22,43 pg/dl dan kelompok plasebo 71,11 pg/dl (p:0,045). Rerata rasio IL-6 pada kelompok herbal 1142,16% sedangkan pada kelompok plasebo 754,45% (p:0,052).Simpulan: Ekstrak herbal penurun asam urat dapat menurunkan kadar IL-6 serum penderita hiperurisemia.
Peran Limfosit T Helper-1 (TH1) dan T Helper-2 (TH2) pada Patogenesis Artritis Lepra Hadi, Suyanto; Sunarto, Sunarto; S, Hardyanto; Triyuliati, Triyuliati; J, Susanto; Hartono, F.X.
MEDIA MEDIKA INDONESIANA 2008:MMI Volume 43 Issue 1 Year 2008
Publisher : MEDIA MEDIKA INDONESIANA

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ABSTRACTThe role of lymphocyte T Helper-1 (TH1) and T Helper-2 (TH2) in the pathogenesis of leprosy arthritisBackground: The autoreactive of TH CD4+ cells is the thought to play an important role in arthritis leprosy pathogenesis. However, wheter of TH1 or TH2 predominant has never been studied.Methods: Various Ag M. leprae (Ag 35 kDa, 10 kDa, 45 kDa, 85 kDa, and MLSA 2 ug/ml) were stimulated to the peripheral blood (10cc) lymphocyte culture (PBMC) using 96 weels microplate and RPMI 1640 media of 22 leprosy arthritis cases, control-1 (n=12) (leprosy without arthritis) and control 2 (n=12) (healthy contact). The activity difference between TH1 and TH2 CD4+ lymphocyte was analysed using the difference delta levels of IFN-γ and IL-4 (ELISA) of the three group studies. Statistical analysis used wereANOVA, Kruskal Wallis or Mann Whitney, and Chi-square.Results: IFN-γ delta levels was significantly higher in the lymphocytes cultures in LA group (the median 132.234 pg/ml, 60.347 g/ml, 14.093 pg/ml, 16.619 pg/ml and 138.394 pg/ml) compared with IL-4 value level (median 0.317 pg/ml, 0.017 pg/ml, -0.206 pg/ml, -0.200 pg/ml and 0.492 pg/ml) after being stimulated with 35 kDa, 10 kDa MMP-1, 45 kDa LAM, 85 kDa and MLSA of 2 ug/ml dose consecutively (all p<0.001). The IFN-γ delta value in LA group also showed the significantly higher level in response toall M. leprae Ag compared to all control-groups, with all p value < 0.05.Conclusion: TH1 CD4+ lymphocyte activity is more dominant compared than TH2 CD4+ lymphocyte activity in leprosy arthritis group patients.Key Words: Leprosy arthritis, IFN-γ, IL-4, TH1 CD4+ and TH2 CD4+ lymphocyte, and M. leprae Ag ABSTRAKLatar belakang: TH CD4+ autoreactive diduga kuat pada patogenesis artritis lepra. Apakah autoimunitas akibat dominansi aktivasi limfosit TH1 atau TH2 pada penderita lepra belum pernah diteliti.Metode: Berbagai Ag M.leprae (35 kDa, 10 kDa, 45 kDa LAM, 85 kDa, dan MLSA dosis 2 ug/ml) distimulasikan pada kultur limfosit darah perifer (10 cc darah vena), menggunakan media RPMI 1640 dari 22 kasus artritis lepra, 12 kontrol-1 (lepra tanpa artritis), dan 12 kontrol-2 (tetangga sehat kontak positif). Nilai delta kadar IFN-γ dan IL-4 (ELISA) diukur untuk mengetahui peran aktivitas limfosit TH1 dan TH2. Statistik yang dipergunakan uji ANOVA, uji Kruskal-Wallis atau Mann Whitney, dan metode Chi-square.Hasil: Nilai delta IFN-γ kultur limfosit kasus artritis lepra (median 132,234 pg/ml, 60,347 pg/ml, 14,093 pg/ml, 16,619 pg/ml dan 138,394 pg/ml) kelompok LA lebih tinggi bermakna dibandingkan nilai delta IL-4 (median 0,317 pg/ml, 0,017 pg/ml, -0,206 pg/ml, - 0,200 pg/ml dan 0,492 pg/ml) pasca stimulasi dengan Ag M. leprae 35 kDa, 10 kDa MMP-1, 45 kDa LAM, 85 kDa dan MLSA dosis 2 ug/ml, (p<0,001). Nilai delta IFN-γ kelompok kasus juga lebih tinggi dibandingkan kedua kelompok kontrol (p< 0,05).Simpulan: Aktivitas limfosit TH1 CD4+ lebih dominan dibandingkan TH2CD4+ pada kelompok penderita artritis lepra.
Hyperuricemia and Pro Inflammatory Cytokine (IL-1β, IL-6, and TNF-α) Hadi, Suyanto; Sudarsono, D; Suntoko, Bantar
Indonesian Journal of Rheumatology Vol 2, No 1 (2010)
Publisher : Indonesian Rheumatology Association

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Background. Rugerio et al 2006 reported that there were a positive correlation between the level of hyperuricemia and the level of IL-1β, IL-6, and TNF-α pro infl ammatory cytokines value. On the other hand, Choi et al reported a negative correlation between hyperuricemia and the level of pro infl ammatory cytokine in the late phase of hyperuricemia.Methods. Venous blood samples were collected and stored at a temperature of - 80oC from in- and outpatients with hyperuricemia with age of more than 17years old at Dr. Kariadi Hospital, Semarang. The level of uric acids (mg/dl) were examined with enzymatic colorimetric technique (Roche Diagnostics) whereasthe levels of IL-1β, IL-6, and TNF-α pro infl ammatory cytokines (pg/ml) were examined with enzyme linked immunosorbent assay (ELISA) technique using ultrasensitive commercial kit (Human ultra sensitive, Biosource International Inc Europe), and ELX 800, 2002 machine. The normality of the data was tested withOne-Sample Kolmogorov-Smirnov technique and the correlation was tested with Spearman correlation (data with abnormal distribution) or Pearson correlation (datawith normal distribution).Results. There was a weak positive correlation between the level of hyperuricemia and the level of IL-1 β cytokine in Spearman correlation test with r value = 0.246 and p value > 0.05 in Spearman correlation test. On the other hand, there was a weak negative correlation between the level of hyperuricemia and the level of TNF-α cytokine with r value = - 0.096 and p value > 0.05. There was also weak negative correlation between the level of hyperuricemia and the level of IL-6 cytokine with r value = - 0.072 and p value > 0.05 in Pearson correlation test.Conclusion. There was a weak positive correlation but not sifnificant between the level of hyperuricemia and the level of IL-1β.
Hyperuricemia and Pro Inflammatory Cytokine (IL-1β, IL-6, and TNF-α) Hadi, Suyanto; Sudarsono, D; Suntoko, Bantar
Indonesian Journal of Rheumatology Vol 2 No 1 (2010)
Publisher : Indonesian Rheumatology Association

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Abstract

Background. Rugerio et al 2006 reported that there were a positive correlation between the level of hyperuricemia and the level of IL-1β, IL-6, and TNF-α pro infl ammatory cytokines value. On the other hand, Choi et al reported a negative correlation between hyperuricemia and the level of pro infl ammatory cytokine in the late phase of hyperuricemia.Methods. Venous blood samples were collected and stored at a temperature of - 80oC from in- and outpatients with hyperuricemia with age of more than 17years old at Dr. Kariadi Hospital, Semarang. The level of uric acids (mg/dl) were examined with enzymatic colorimetric technique (Roche Diagnostics) whereasthe levels of IL-1β, IL-6, and TNF-α pro infl ammatory cytokines (pg/ml) were examined with enzyme linked immunosorbent assay (ELISA) technique using ultrasensitive commercial kit (Human ultra sensitive, Biosource International Inc Europe), and ELX 800, 2002 machine. The normality of the data was tested withOne-Sample Kolmogorov-Smirnov technique and the correlation was tested with Spearman correlation (data with abnormal distribution) or Pearson correlation (datawith normal distribution).Results. There was a weak positive correlation between the level of hyperuricemia and the level of IL-1 β cytokine in Spearman correlation test with r value = 0.246 and p value > 0.05 in Spearman correlation test. On the other hand, there was a weak negative correlation between the level of hyperuricemia and the level of TNF-α cytokine with r value = - 0.096 and p value > 0.05. There was also weak negative correlation between the level of hyperuricemia and the level of IL-6 cytokine with r value = - 0.072 and p value > 0.05 in Pearson correlation test.Conclusion. There was a weak positive correlation but not sifnificant between the level of hyperuricemia and the level of IL-1β.
Kadar IFN-γ (fungsi TH-1 CD4+) dan IL-4 (Fungsi TH-2 CD4+) pada Penderita Artritis Lepra Hadi, Suyanto; Triyuliati, Triyuliati
MEDIA MEDIKA INDONESIANA 2010:MMI VOLUME 44 ISSUE 1 YEAR 2010
Publisher : MEDIA MEDIKA INDONESIANA

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The correlation between IFN-γ (TH-1 CD4+ function) and IL-4 level (TH-2 CD4+ function) in leprosy arthritisBackground: It was hypothesized by some expertise that there is a negative correlation between TH-1 CD4+ function (IFN- level) and TH-2 CD4+ function (IL-4 level) in rheumatoid arthritis and lupus pathogenesis (Leader). The correlation between IFN-γ level and IL-4 level in the leprosy arthritis has never been reported. The objective of the study is to evaluate the correlate between IFN- and IL-4 level in leprosy arthritis. Method: The correlation between IFN- level (pg/ml) and IL-4 level (pg/ml) were analysed after stimulated with several M. leprae Ag. (10 kDa, 35 kDa, and MLSA 2 ug/ml) on the peripheral blood lymphocyte culture of leprosy arthritis patients (n=22) (RPMI 1640 sigma). The study was carried out at Hayati Laboratory Gajah Mada University. The Spearman correlation test was used in analysis.Result: There were no significant correlations between IFN- and IL-4 level given 3 different numbers of M. leprae with r1=-0.32, r2=0.262, and r3=0.324 with p1=0.888, p2=0.238, and p3=0.747 respectively of Spearman test on arthritis leprosy group. Conclusion: There is no correlation between IFN- and IL-4 level in leprosy arthritis patients.ABSTRAKLatar belakang: Dihipotesiskan oleh para ahli adanya korelasi negatif antara fungsi limfosit TH1CD4+ (kadar IFN- pg/ml) dan limfosit TH-2 CD4+ (kadar IL-4 pg/ml) pada artritis reumatoid dan lupus eritematosus sistemik (Leader). Korelasi kadar IFN-γ (pg/ml) dan kadar IL-4 (pg/ml) pada artritis lepra belum pernah dilaporkan. Penelitian ini bertujuan untuk mengevaluasi korelasi antara kadar IFN- dan IL-4 pada penderita artritis lepra.Metode: Metode penelitian yang dipergunakan adalah belah lintang. Dilakukan analisis hubungan kadar IFN- (pg/ml) dan IL-4 (pg/ml) pada kultur limfosit darah perifer (RPMI 1640 sigma) penderita artritis lepra pasca stimulasi beberapa Ag M. leprae (10 kDa, 35 kDa, dan MLSA 2 ug/ml). Kultur limfosit darah dilakukan di Laboratorium Hayati FK UGM Yogyakarta. Dilakukan uji korelasi dengan Spearman. Hasil: Tidak terdapat korelasi antara kadar IFN- (pg/ml) dengan kadar IL-4 (pg/ml) setelah distimulasi dengan dosis berbeda, dengan nilai r1=-0,32, r2=0,262, dan r3=0,324 berturut-turut disertai nilai p1=0,888, p2=0,238, dan p3=0,747 dengan uji korelasi Spearman. Simpulan: Tidak terdapat korelasi antara kadar IFN-γ dengan IL-4 pada kultur limfosit darah perifer penderita artritis lepra