A pilot study of daily subcutaneous interleukin-10 in patients with chronic hepatitis C infection

The Th1/Th2 cytokine balance is important in persistence of infection and l iver injury in chronic hepatitis C. The aim of this study was to administer the anti-inflammatory cytokine, recombinant human interleukin-10 (rHuIL-10 ), for 28 days in patients with chronic hepatitis C and to assess the safet y and measure the effect on alanine aminotransferase (ALT, a marker of hepa tic inflammation) levels and serum hepatitis C virus (HCV) RNA values. Thre e treatment-naive and 13 interferon (IFN) nonresponder patients (total 16 p atients) with compensated chronic HCV infection were enrolled in this study . Patients were randomized to receive rHuIL-10 at a dose of 4 or 8 mu g/kg/ day as a single daily subcutaneous injection for 28 days. ALT values and se rum HCV RNA were measured at days 0, 1, 3, 8, 15, 22, and 28 during therapy and at follow-up 2 and 4 weeks after cessation of the 4-week treatment per iod. ALT values normalized in 9 of 16 patients during therapy and remained normal until the end of treatment in 8 patients. The decreases in ALT value s occurred in both the 4 lug and 8 lug dosage groups and were seen in both IFN naive and nonresponder patients. Mean ALT values fell significantly dur ing the study period but usually returned to pretreatment levels by the end of the 4-week follow-up period (p < 0.05). HCV RNA concentrations did not vary significantly during or after therapy. (No patient had either an incre ase or a decrease in HCV RNA levels of greater than or equal to 1.5 log dur ing the study.) The drug was well tolerated, with no adverse symptoms noted . Platelet counts fell transiently to 73,000 and 63,000 in 2 patients. No o ther toxicity was observed, and no patients discontinued therapy. In chroni c hepatitis C, short-term therapy with IL-10 was well tolerated and caused transient normalization of ALT values in 50% of patients, which returned to pretreatment levels on cessation of treatment. There were no significant c hanges observed in serum HCV RNA concentrations during the study. These imm unomodulatory effects are similar to those observed with ribavirin monother apy in chronic hepatitis C. Further study of rHuIL-10 alone or in combinati on with antiviral agents in chronic hepatitis C is warranted.