title: Long-term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti-inflammatory effect.
abstract: An imbalance in Th1 and Th2 cytokine production is implicated in disease progression of HCV. Our aim was to determine the effect of IL-10 administration in patients with HCV-related liver disease. Thirty patients with advanced fibrosis who had failed antiviral therapy were enrolled in a 12-month treatment regimen with SQ IL-10 given daily or thrice weekly. Liver biopsies were performed before and after therapy. Serum and PBMC were collected for HCV RNA, ALT, and functional T-cell analysis. IL-10 led to significant improvement in serum ALT (mean ALT: day 0 = 142 +/- 17 vs. month 12 = 75 +/- 10; P <.05). Hepatic inflammation score decreased by at least 2 in 13 of 28 patients (mean decrease from 4.6 +/- 0.3 to 3.7 +/- 0.3, P <.05) and 11 of 28 showed a reduction in fibrosis score (mean change from 5.0 +/- 0.2 to 4.5 +/- 0.3, P <.05). Serum HCV RNA levels increased by 0.5 log during therapy (mean HCV RNA day 0: 12.3 +/- 3.0 Meq/mL; 12 months: 38 Meq/mL; P <.05) and returned to baseline at the end of follow-up (11.0 +/- 2.4 Meq/mL). Five patients developed viral loads of greater than 120 Meq/mL and two of these developed an acute flare in serum ALT. IL-10 caused a decrease in the number of HCV-specific CD4+ and CD8+ IFN-gamma secreting T cells and alterations in PBMC cytokine production towards a Th2 dominant profile. These changes parallel the improvement in ALT and rise in HCV RNA. In conclusion, long-term rIL-10 therapy appears to decrease disease activity, but also leads to increased HCV viral burden via alterations in immunologic viral surveillance.
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects*; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D012367:RNA, Viral; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins; D016753:Interleukin-10; D007371:Interferon-gamma; D000410:Alanine Transaminase