INDUCTION OF INTERLEUKIN-6 BY INTERFERON-ALFA AND ITS ABROGATION BY ASERINE-PROTEASE INHIBITOR IN PATIENTS WITH CHRONIC HEPATITIS-C

We investigated short-term alterations in plasma interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF- alpha) levels induced by interferon alfa (IFN-alpha) injection in 18 p atients with chronic hepatitis C. A single intramuscular injection of human recombinant IFN-alpha 2a (6 million units [MU]) significantly in creased the plasma IL-6 level 6 hours after the injection (P < .05), O n the other hand, the IFN-alpha injection did not affect the plasma TN F-alpha and IL-1 beta levels. Polymerase chain reaction (PCR) analysis showed accumulation of IL-6 gene transcripts in peripheral blood mono nuclear cells (PBMC) after IFN-alpha injection, indicating that IFN-al pha enhances IL-6 production at the messenger RNA level. The induction of IL-6 by IFN-alpha was completely suppressed by the intravenous adm inistration of gabexate mesilate (GM), a serine protease inhibitor. Th e mechanism whereby GM suppresses the elevation in circulating IL-6 le vels seems to be the inhibition of IL-6 production at the messenger RN A level, Elevations of both serum C-reactive protein (CRP) levels and body temperature after GM-suppressed IFN-alpha injection suggest that the administration of GM, by suppressing IL-6 production, may attenuat e the IL-6-related responses induced by IFN-alpha injection. In conclu sion, we found that IL-6 was induced by IFN-alpha in vivo and that thi s induction was completely abrogated by the administration of GM. Our results indicate that serine protease inhibitors may be useful for inh ibiting IL-6-relating responses.