Proinflammatory Cytokines Inhibit HIV-1SF162 Expression in Acutely Infected Human Brain Cell Cultures

James R Lokensgard, Genya Gekker, Laura C. Ehrlich, Shuxian Hu, Chun C. Chao, Phillip K. Peterson

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41 Scopus citations

Abstract

An understanding of how viral replication in glial cells responds to proinflammatory cytokines is important in delineating HIV-1 neuropathogenesis. Because no information is available in the literature regarding the regulatory effects of exogenous cytokines on acute HIV-1 replication in human brain cells, we studied the impact of cytokine treatment on viral p24 Ag expression. Based upon reports using mononuclear phagocytes derived from somatic sources, we hypothesized that TNF-α, IL-1β, and IL-6 would up-regulate the expression of HIV-1SF162 (a monocytotropic strain) in purified microglial cells and in mixed brain cell cultures. This hypothesis was not supported. In fact, a contrary, unexpected result was obtained; whereas in purified microglial cultures TNF-α displayed a mild stimulatory effect on HIV-1 expression (15% increase in p24 Ag production compared with control cultures), surprisingly, IL-1β and IL-6 were highly suppressive (91 and 83% inhibition of HIV expression, respectively). In contrast to the findings in microglial cell cultures, TNF-α profoundly suppressed (84%) HIV-1 expression in mixed brain cell cultures, as did IL-1β (82%), and IL-6 was moderately suppressive (55% inhibition). In an attempt to identify factors responsible for the differential effects of TNF-α in the two brain cell infection models, it was found that compared with microglial cell cultures, TNF-α treatment of mixed brain cell cultures released significantly greater amounts of RANTES (regulated upon activation, normal T cell expressed and secreted) and macrophage inflammatory protein-1α, β-chemokines that have been suggested to have anti-HIV-1 effects. Thus, these data suggest that proinflammatory cytokines possess anti-HIV-1 activity in the central nervous system.

Original languageEnglish (US)
Pages (from-to)2449-2455
Number of pages7
JournalJournal of Immunology
Volume158
Issue number5
StatePublished - Mar 1 1997

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