Interleukin 10 treatment reduces fibrosis in patients with chronic hepatitis C: a pilot trial of interferon nonresponders.
OBJECTIVE
Interleukin (IL)-10 is a cytokine that down-regulates the proinflammatory response and has a modulatory effect on hepatic fibrogenesis. The aim of this study was to determine the effect of IL-10 on hepatic injury in patients with chronic hepatitis C.


METHODS
Twenty-four patients with chronic hepatitis C who had not previously responded to interferon-based therapy were enrolled in a randomized, double-blinded 2-dose trial in which they received either 4 or 8 microgram/kg IL-10 subcutaneously daily for 90 days. Liver biopsies were performed before and at the end of therapy.


RESULTS
IL-10 was well tolerated with 22 patients completing the study. Serum ALT levels normalized in 19 of 22 patients by the end of therapy and were sustained in 5 of 22. Hepatic inflammation decreased in 19 of 22 patients, with 11 having a decrease by >/=2. Fibrosis decreased in 14 of 22 patients (mean change, 3.6-2.6; P = 0.001). There was no change in serum HCV RNA levels. IL-10 therapy was associated with changes in serological markers, suggesting a reduction of immune response and fibrogenesis.


CONCLUSIONS
IL-10 therapy is safe and well tolerated in patients with chronic hepatitis C. Although it has no apparent antiviral activity, IL-10 normalizes serum ALT levels, improves liver histology, and reduces liver fibrosis in a large proportion of patients receiving treatment. Therefore, IL-10 may have therapeutic potential in patients with chronic hepatitis C patients who do not respond to interferon-based therapy.
Nelson
D R
DR
Section of Hepatobiliary Diseases and Department of Pathology, University of Florida College of Medicine, Gainesville, Florida, USA. nelsodr@medicine.ufl.edu
Lauwers
G Y
GY
Lau
J Y
JY
Davis
G L
GL
D000410:Alanine Transaminase / Q000097:blood; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000473:pathology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D016753:Interleukin-10 / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016207:Cytokines; D012367:RNA, Viral; D011994:Recombinant Proteins; D016753:Interleukin-10; D007372:Interferons; D000410:Alanine Transaminase