Complex effects of interferon-alpha on the cytokine network in HIV infection--possible contribution to immunosuppression.
Since interleukin (IL-)2, IL-10 and IL-12 may contribute to the pathogenesis of human immune deficiency virus (HIV) infection we examined the effect of interferon (IFN)-alpha on these cytokines in cultures of various subsets of peripheral blood mononuclear cells (PBMC) in ten HIV-infected patients and ten healthy controls. Our main findings were: (1) IFN-alpha markedly enhanced IL-10 levels in a dose-dependent manner in both lipopolysaccharide (LPS)- and phytohaemagglutinin (PHA)-stimulated PBMC, as well as in anti-CD3- and anti-CD3/anti-CD28-stimulated T cells in both HIV-infected patients and controls. (2) In contrast, IFN-alpha had a downregulatory effect on IL-10 levels in Candida -stimulated PBMC,with particularly strong suppressive effect in HIV-infected patients. (3) Furthermore, IFN-alpha had a significant but modest stimulatory effect on IL-2 levels in PHA- and Candida -stimulated PBMC and anti-CD3-stimulated T cells. (4) IFN-alpha enhanced IL-12 levels in a dose-dependent manner in LPS-stimulated PBMC in both patients and controls. Our findings that IFN-alpha markedly enhanced IL-10 and modestly enhanced IL-2 and IL-12, suggest a net immunosuppressive effect of IFN-alpha in HIV-infected patients, possibly contributing to progression of immunodeficiency in these patients.
Stylianou
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Section of Clinical Immunology and Infectious Diseases and Research Institute for Internal Medicine, Medical Department, Rikshospitalet, Oslo, N-0027, Norway. eva.stylianou@klinmed.uio.no
Aukrust
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P
Müller
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F
Nordøy
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I
Frøland
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SS
D000328:Adult; D000368:Aged; D002176:Candida albicans / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007124:Immunoenzyme Techniques; D016898:Interferon-alpha / Q000009:adverse effects / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000821:virology
D016207:Cytokines; D016898:Interferon-alpha; D007376:Interleukin-2; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D016753:Interleukin-10; D018664:Interleukin-12