ALTERED PRODUCTION OF PGE(2), IL-1-BETA AND TNF-ALPHA BY PERIPHERAL-BLOOD MONOCYTES FROM HIV-POSITIVE INDIVIDUALS AT EARLY STAGES OF HIV-INFECTION

We analyzed the in vitro synthesis and release of PGE2, IL-1beta, and TNF-alpha by peripheral blood monocytes from HIV-infected injection dr ug users at the early clinical stages of HIV infection. We investigate d whether there is a concomitant altered production of PGE2 and proinf lammatory cytokines by HIV-positive monocytes. We also evaluated T-cel l subsets and lymphocyte transformation response to pokeweed mitogen ( PWM) in HIV-positive patients and healthy controls. PGE2 and IL-1beta levels in supernatants from monocyte cultures were determined by radio immunoassay (RIA), and TNF-alpha by enzyme immunoassay (EIA). Monocyte s from asymptomatic HIV-positive individuals produced spontaneous and significantly increased quantities of PGE2, IL-1beta, and TNF-alpha. C oncomitant increased production of PGE2 and IL-1beta by monocytes from HIV-positive asymptomatic patients was significantly associated with low CD4+ T-cell numbers (<500 cells/mm3). We also found a strong assoc iation between spontaneous and concomitantly increased production of P GE2 and cytokines by monocytes from asymptomatic HIV-positive individu als and a low lymphocyte transformation response to PWM. Further studi es are necessary to establish whether this altered production of PGE2 and proinflammatory cytokines by monocytes from HIV-positive individua ls might play a role in the mechanisms involved in the progressive imp airment of cell-mediated immunity in HIV infection.