TENIDAP INHIBITS REPLICATION OF THE HUMAN IMMUNODEFICIENCY VIRUS-1 INCULTURED-CELLS

Interleukin-6 (IL-6) may be important in the pathogenesis of HIV-1 bec ause of its ability to induce HIV-1 expression in infected cells in vi tro. Tenidap, a structurally and functionally novel antirheumatic drug affecting diverse biologic processes, has been shown to reduce IL-6 p roduction by peripheral blood mononuclear cells stimulated with lipopo lysaccharide. Tenidap also inhibits the activity of chloride-bicarbona te exchangers and causes acidification of the cytoplasmic compartment that is similar to the effect of the anion transport inhibitor UK5099. Furthermore, tenidap inhibits the cyclooxygenase-mediated pathway of arachidonic acid metabolism as do the nonsteroidal antiinflammatory dr ugs (NSAIDs). Here we show that tenidap decreased HIV-1 replication as measured by p24 core antigen in the acutely infected CD4(+) T-lymphoc yte lines H9 and Jurkat, in the acutely infected monocyte line U937, a nd in its chronically infected subclone U1.8/HIV. These effects were s een at concentrations in the range of 3 to 15 mu M, well below those t oxic to cells. The antiviral effects of tenidap may be independent of its ability to reduce IL-6 production based on the observations that t hese effects were as prominent in IL-6 nonresponsive lines as in IL-6 responsive lines and that the inhibition of p24 production was not rev ersed by exogenous IL-6.