Autoregulatory role of interleukin-10 in hepatitis C patients treated with IFN-alpha.
Interferon-alpha2 (IFN-alpha2) is used as standard treatment of patients with chronic hepatitis C (cHCV), but little is known about the immunomodulatory effects of this cytokine in vivo. We have studied immunologic parameters in freshly isolated peripheral blood mononuclear cells (PBMC) of 26 patients with cHCV 12 h before and 12 h after the first s.c. injection of 5-6 MU IFN-alpha2. In PBMC obtained after IFN injection, a substantial increase in IL-10 production after antigen-specific and nonspecific stimulation was observed, whereas IFN-gamma production and proliferation were significantly diminished compared with PBMC obtained before IFN injection. Patients were stratified according to single nucleotide polymorphisms (SNPs) in the interleukin-10 (IL-10) promoter, which have been associated with the response to IFN therapy. Induction of IL-10 and suppression of IFN-gamma levels were more prominent in patients with genotype CC at position -592 (n = 15) compared with patients with genotype AA/AC (n = 11). In conclusion, our data indicate that IFN-alpha2 therapy can potently enhance IL-10 and suppress IFN-gamma production of PBMC, which is, at least partially, dependent on an SNP in the IL-10 promoter. This suggests an autoregulatory role of IL-10 in IFN therapy.
Luik
Armin
A
University of Mainz, Department of Medicine, 55101 Mainz, Germany.
Knapp
Susanne
S
Thursz
Mark
M
Thomas
Howard C
HC
Schlaak
Jörg F
JF
D000328:Adult; D000368:Aged; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006706:Homeostasis; D006801:Humans; D066298:In Vitro Techniques; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma; D004247:DNA