Cytokines and Chemokines in HIV Infection: Implications for Therapy

HIV infection is associated with both a hyperactivity of the immune system and decreased immune responses against specific antigens. A similar pattern is observed when considering cytokine production in HIV-infected patients. Several cytokines are spontaneously produced at an increased level, whereas other cytokines playing an important role during cell-mediated immune responses are produced at a low level following stimulation. This deregulation of cytokine production may participate to the immune deficiency, both by impairing immune responses and by accelerating CD4+ T lymphocyte destruction. Chemokine receptors have recently been shown to function as coreceptors for the virus, and to govern its cellular tropism. Heterogeneous expression of chemokine receptor may contribute to differences in infectability as well as in rate of progression of the disease between individuals. Better understanding of the role of cytokines and chemokines in HIV infection suggests new therapeutic approaches where administration of cytokines or cytokine antagonists may allow the immune system to function in better conditions, to stimulate antiviral and antiinfectious immune defenses, and to limit viral spread.