Cytokine gene expression occurs more rapidly in stimulated peripheral blood mononuclear cells from human immunodeficiency virus-infected persons

Evaluation of cytokine gene expression following in vitro stimulation is on e means of examining the dysregulation of the immune system in human immuno deficiency virus (HIV) infection. We have assessed differences in the immun e status of non-HIV-infected (HIV-) and HIV-infected (HIV+) individuals by evaluating the kinetics of the expression of cytokine genes, We compared de tailed time courses of cytokine mRNA expression in HIV- and HIVS peripheral blood mononuclear cells (PBMC) and found that there is a significant shift (P < 0.01) for all cytokines examined (interleukin 2 [IL-2], IL-6, IL-10, gamma interferon, and tumor necrosis factor alpha [TNF-alpha]) to an earlie r time of mean peak mRNA expression by HIV+ PBMC (betcveen 4 and 8 h) compa red to HIV- PBMC (8 h) in response to either phytohemagglutinin (PHA) or an ti-CD3 stimulation. Additional studies showed that although PHA stimulated HIV+ PBMC showed decreased median IL-2, IL-4, and TNF-alpha mRNA levels, th ey typically demonstrated more rapid kinetics (increased mean 4-h/24-h cyto kine mRNA ratios), with significant differences for IL-4 (P < 0.05) and TNF -alpha (P < 0.005), compared to HIV- PBMC. The use of fresh or frozen cells gave comparable cytokine mRNA data; however, the secretion of some cytokin e proteins (IL-2 receptor, IL-10, and TNF-alpha) appeared to be reduced in HIV+ PBMC that had been frozen and thawed. Our studies demonstrate that the kinetics of cytokine gene expression can reveal additional dysregulation o f the immune system in HIV infection, suggesting that PBMC of HIV-infected persons exist in an activated state in vivo that permits them to express cy tokine genes more rapidly than a normal PBMC.