Abstract 947 Poster Session IV, Tuesday, 5/4 (poster 114)

There is significant evidence, from in vitro and in vivo studies, that astrocytes and cytokines are intimately involved in HIV neuropathogenesis. However, it is not yet clear whether astrocytes must be infected by HIV before these cells express cytokines or whether physical contact between HIV and astrocytes is sufficient. In this study, we used RT-PCR and ELISA to examine mRNA and protein expression of the pro-inflammatory cytokines IL-1, IL-6, TNF-alpha, INF-gamma and TGF-beta in primary cultures of fetal human astrocytes after they were treated with purified/unpurified HIV-1, gp120/gp160, INF-gamma or LPS. The kinetics of cytokine expression by unpurified HIV and INF-gamma were similar to LPS treated astrocytes in both short-term. Neither purified HIV nor gp120/gp160 induced astrocytes to express significant amounts of the cytokines mentioned above during the first three days of culture. However, LPS, INF-gamma, TNF-alpha and IL-1beta induced cytokine expression during this period. Upon prolonged culturing of astrocytes with purified HIV and demonstration of cellular infection, cytokines were detected and their expression increased positively with p24 concentrations. In contrast, neither short nor extended exposure times with heat inactivated HIV demonstrated increases in cytokine expression. These results demonstrate that astrocytes may be a potential source of pro-inflammatory cytokines during HIV replication in nervous system tissue.

This work was supported, in part, by USPHS grant MH46815 and Children's Hospital of Michigan Endowment Fund