The Role of Cytokines and Chemokines in HIV Disease at the Verge of the New Millennium

The human immunodeficiency virus (HIV) is the causative agent of the acquired immunodeficiency syndrome (AIDS). Its replication is controlled by the homeostatic network of cytokines and chemokines that can affect multiple steps in the virus life cycle. Proinflammatory cytokines usually potentiate HIV production via activation of cellular transcription factors, such as NF-kB or NFAT. Interleukin-6 (IL-6) and interferon-ɤ (IFN-ɤ) upregulate HIV expression by acting predominantly at post-transcriptional levels. Antiinflammatory cytokines such as transforming growth factor-s (TGF-s) and IL-10 can potentiate but also inhibit viral replication. Chemokines compete with the virus for cell surface 7-transmembrane domain receptors also acting as entry co-receptors for HIV together with CD4. IL-2 is under scrutiny for the experimental therapy of HIV disease because of its unique ability of raising the number of circulating CD4+ T lymphocytes to normal or near normal levels.