MODULATION OF HIV-1 REPLICATION BY CYTOKINES AND SOLUBLE CYTOKINE RECEPTORS

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Cytokines are cell-derived proteins that function as hormones in the immune system and affect cellular growth and differentiation. Their effects on human cells enable cytokines to modulate replication of HIV-1. We are determining the effects of various cytokines on HIV replication in lymphocytes and monocytes, cells involved in the immune response and also susceptible to infection with HIV. Since the ability to control cytokine-mediated modification of HIV replication is important therapeutically, we are studying the ability of natural antagonists to control modulation of HIV replication by cytokines. We have shown that replication of HIV in human cells can be induced by the cytokine, TNF-a, and that this induction can be reversed by using soluble TNF receptors. We now find that selenium can modulate TNF effects on HIV replication in chronically infected MO and T cells, but only on acute infection of MO. We also find that IFN-a species/components vary in their ability to inhibit HIV replication, which may facilitate selection of a less toxic IFN-a that can be used in vivo. The work ongoing in my laboratory is directed at understanding how existing networks involving cytokines and/or their soluble receptors function in vitro and in vivo. An understanding of this mechanism allows for a more detailed and scientific approach to the review of new products, both cytokines and soluble cytokine receptors, proposed for therapeutic use as antagonists to cytokine activity in vivo. Since my laboratory has shown that a delicate balance exists between cytokines and their antagonists, such that both enhancement and inhibition of cytokine biologic activity can result by altering their concentrations, it sheds new light on the complexities that exist for the proposed therapeutic use of these agents. Our findings may also assist in determining what parameters to monitor in patients that are receiving either cytokines or soluble cytokine receptors.