Papaverine hydrochloride: effects on HIV replication and T-lymphocyte cell function.

Papaverine hydrochloride (PAP) has previously been shown to have a potent inhibitory effect on the replication of viruses such as cytomegalovirus (CMV) and measles. In this report the effect of PAP on human immunodeficiency virus (HIV) replication and T lymphocyte cell function were examined. MT4 cells infected with HIV strain 3b were incubated with serial dilutions of PAP (1-30 microM). At selected times postinfection HIV replication was measured by reverse transcriptase activity (RT) or HIV p24 Ag. PAP significantly inhibited HIV replication by more than 99% at doses of 30 microM with an CD50 and ED50 of 32 microM and 5.8 microM respectively. The mechanism of inhibition of HIV caused by PAP appeared independent form its ability to increase intracellular levels of cAMP and was not mediated via a direct effect on RT activity. To examine T cell function, peripheral blood mononuclear cells (PBMC) from normal donors were stimulated with phytohemagglutinin (PHA) or CMV Ag in the presence or absence of PAP (1-30 microM). At selected times proliferative response to PHA and CMV Ag were determined by [3H]thymidine uptake. In addition, interferon (IFN) gamma and interleukin 2 (IL2) response to mitogens were measured by radioimmunoassay (RIA). PAP enhanced PHA induced IFN production at doses of 1-10 microM and CMV Ag induced IFN production at doses of 1-3 microM. Higher doses were inhibitory. PAP did not affect IL-2 production or IL2 receptor expression and had an inhibitory effect on mitogenic responses.