Induction of interleukin-6 by interferon alfa and its abrogation by a serine protease inhibitor in patients with chronic hepatitis C.
We investigated short-term alterations in plasma interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha) levels induced by interferon alfa (IFN-alpha) injection in 18 patients with chronic hepatitis C. A single intramuscular injection of human recombinant IFN-alpha 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-alpha injection did not affect the plasma TNF-alpha and IL-lbeta levels. Polymerase chain reaction (PCR) analysis showed accumulation of IL-6 gene transcripts in peripheral blood mononuclear cells (PBMC) after IFN-alpha injection, indicating that IFN-alpha enhances IL-6 production at the messenger RNA level. The induction of IL-6 by IFN-alpha 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-alpha injection suggest that the administration of GM by suppressing IL-6 production, may attenuate the IL-6-related responses induced by IFN-alpha injection. In conclusion, we found that IL-6 was induced by IFN-alpha 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.
Ito
N
N
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Kawata
S
S
Tamura
S
S
Kiso
S
S
Tsushima
H
H
Maeda
Y
Y
Yamasaki
E
E
Igura
T
T
Matsuzawa
Y
Y
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002908:Chronic Disease; D005260:Female; D016670:Gabexate / Q000494:pharmacology*; D006526:Hepatitis C / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000097:blood / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D016898:Interferon-alpha; D015850:Interleukin-6; D012367:RNA, Viral; D015842:Serine Proteinase Inhibitors; D016670:Gabexate; D015088:2',5'-Oligoadenylate Synthetase