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 pathogenesi s of human immune deficiency virus (HIV) infection we examined the effect o f interferon (IFN)-alpha on these cytokines in cultures of various subsets of peripheral blood mononuclear cells (PBMC) in ten HIV-infected patients a nd ten healthy controls, Our main findings were: (1) IFN-alpha markedly enh anced IL-10 levels in a dose-dependent manner in both lipopolysaccharide (L PS)- and phytohaemagglutinin (PHA)-stimulated PBMC, as well as in anti-CD3- and anti-CD3/anti-CD28-stimulated T cells in both HIV-infected patients an d controls, (2) In contrast, IFN-alpha had a downregulatory effect on IL-10 levels in Candida-stimulated PBMC,with particularly strong suppressive eff ect 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 n-12 levels i n a dose-dependent manner in LPS-stimulated PBMC in both patients and contr ols. Our findings that IFN-alpha markedly enhanced IL-10 and modestly enhan ced IL-2 and IL-12, suggest a net immunosuppressive effect of IFN-alpha in HIV-infected patients, possibly contributing to progression of immunodefici ency in these patients. (C) 2001 Academic Press