REGULATION OF CYTOKINE EXPRESSION BY HIV

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Cytokines are a group of cell-derived protein molecules that function as hormones in the immune system and affect cellular growth and differentiation. Cytokines may also serve as a bridge facilitating the interaction between the nervous system and the immune system. In this regard, neurologic abnormalities are frequently observed in HIV-1 infection, which is known to cause an immune deficiency disease. We previously reported that normal human MOs stimulated with the HIV-1 envelope protein, gp120, secrete the vasoconstrictive peptide, ET-1. Due to the consistent presence of macrophages in the brain in HIV neurologic disease, and the biological activity of this cytokine, it is conceivable that ET-1 may cause neurological abnormalities and/or facilitate entry of MOs into the brain. Since dysregulation of cytokine production is observed in HIV infection, other cytokines could also be induced or inhibited in the brain that would contribute to the pathogenesis of neurologic HIV disease. Our data suggest that some of these candidate cytokines may be derived from astrocytic cells. It is generally accepted that one result of HIV infection in vivo is the aberrant production of a number of cytokines. This abnormal expression of cytokines can lead to a variety of clinical manifestations in AIDS. The work ongoing in my laboratory is directed at elucidating the role of various cytokines in HIV infection and correlating their expression with particular disease manifestations. Our results could ultimately lead to new therapeutic approaches directed at regulating the production of particular cytokines or blocking the biological activities, thereby controlling symptoms resulting from aberrant cytokine production. Our findings could also provide new insight with regard to interactions between different biological systems, such as the immune system and the neurologic system, that may contribute to the overall disease process.