Induction of interleukin-6 by interferon alfa and its abrogation by a serine protease inhibitor in patients with chronic hepatitis C

Open Access
Publisher Website
Google Scholar
Abstract
We investigated short‐term alterations in plasma interleukin‐6 (IL‐6), interleukin‐1β (IL‐1β), and tumor necrosis factor α (TNF‐α) levels induced by interferon alfa (IFN‐α) injection in 18 patients with chronic hepatitis C. A single intramuscular injection of human recombinant IFN‐α 2a (6 million units [MU]) significantly increased the plasma IL‐6 level 6 hours after the injection (P < .05). On the other hand, the IFN‐α injection did not affect the plasma TNF‐α and IL‐lβ levels. Polymerase chain reaction (PCR) analysis showed accumulation of IL‐6 gene transcripts in peripheral blood mononuclear cells (PBMC) after IFN‐α injection, indicating that IFN‐α enhances IL‐6 production at the messenger RNA level. The induction of IL‐6 by IFN‐α was completely suppressed by the intravenous administration of gabexate mesilate (GM), a serine protease inhibitor. The mechanism whereby GM suppresses the elevation in circulating IL‐6 levels seems to be the inhibition of IL‐6 production at the messenger RNA level. Elevations of both serum C‐reactive protein (CRP) levels and body temperature after GM‐suppressed IFN‐α injection suggest that the administration of GM by suppressing IL‐6 production, may attenuate the IL‐6‐related responses induced by IFN‐α injection. In conclusion, we found that IL‐6 was induced by IFN‐α in vivo, and that this induction was completely abrogated by the administration of GM. Our results indicate that serine protease inhibitors may be useful for inhibiting IL‐6‐relating responses.

This publication has 0 references indexed in Scilit: