Effects of interferon-α on gene expression of chemokines and members of the tumour necrosis factor superfamily in HIV-infected patients

Abstract

Summary We examined the effect of interferon (IFN)-α on the expression of 375 genes relevant to inflammatory and immunological reactions in peripheral blood mononuclear cells (PBMC) from HIV-infected patients by cDNA expression array and real-time quantitative RT-PCR. Our main findings were: (i) IFN-α induced up-regulation of several genes in the tumour necrosis factor (TNF) superfamily including the ligands APRIL, FasL, TNF-α and TRAIL, with particularly enhancing effects on the latter in HIV-infected patients. (ii) While IFN-α markedly up-regulated the expression of anti-angionetic ELR– CXC-chemokines (e.g. MIG and IP-10), it suppressed the expression of angiogenic ELR+ CXC-chemokines (e.g. GRO-α, IL-8 and ENA-78), with similar patterns in both patients and controls. (iii) IFN-α induced a marked increase in gene expression of the HIV co-receptor CCR5 in both patients and controls. We suggest that these effects may contribute to both the therapeutic and toxic effects of IFN-α. Moreover, our findings underscore that the biological effects of IFN-α in HIV infection are complex and that the clinical net effects of IFN-α treatment may be difficult to predict. However, the potent enhancing effect of IFN-α on several pro-apoptotic genes in the TNF superfamily and the enhancing effect on CCR5 expression suggest a possible pathogenic role of IFN-α in the progression of HIV-related immunodeficiency and suggests caution in the therapeutic use of IFN-α in HIV-infected ­individuals.