Culture supernatants from lipopolysaccharide (LPS)-treated murine microglial cells were found to markedly induce the expression of human immunodeficiency virus (HIV)-1 in the chronically infected human promonocytic cell line U1 as detected by measurements of HIV-1 p24 antigen release into U1 culture supernatants. Antibody to tumor necrosis factor (TNF)-α had an inhibitory effect on the induction of virus by microglial cell supernatants. Also, treatment of microglia with pentoxifylline, an inhibitor of TNF-α production, resulted in suppressed amounts of TNF in the supernatants of LPS-treated microglia and in a reduced stimulatory capacity of these supernatants on HIV-1 expression in U1 cells. These findings support the concept that TNF-α production by glial cells plays a pathogenetic role in HIV-1-associated brain disease by promoting the expression of the virus in infected cells.
Bibliographical noteFunding Information:
We thankK arenClose for technicaal ssistanceD,r . Monica Tsang for providinga ntibodiesD, r. William Novick for helpful discussionsa, nd JacquelineO s-troum for assistancew ith the preparationo f the manuscripTt.h isw orkw ass upporteidn partb y United StatesP ublic Health Service Grants DA-04381 and AI-27661a ndb y grantsfr omH ennepinF acultyA ssoci-atesa ndH oechst-RoussPehl armaceuticaIlnsc, .
- Human immunodeficiency virus-1
- Tumor necrosis factor-α