THE SEROTONIN ANALOG BUSPIRONE INCREASES THE FUNCTION OF PBMC FROM HIV-INFECTED INDIVIDUALS IN-VITRO

HIV infection is characterized by the loss of CD4(+) T cell numbers as well as loss of T cell function leading to severe immunodeficiency. T he proliferative capacity of T cells, measured in vitro as response to antigens and mitogens, is severely reduced during HIV infection. An i ncreased level of the intracellular second messenger cAMP has been dem onstrated to cause impaired proliferative capacity of PBMC from HIV-in fected individuals in vitro. We have identified a serotonin analogue, buspirone, that inhibits the activity of adenylyl cyclase, the enzyme responsible for regulation of intracellular levels of cAMP. Using this inhibitor the proliferative responses of PBMC to a polyclone activato r in vitro were increased in 28/30 HIV-seropositive individuals (p < 0 .00001). Further, we demonstrated that this was due to proliferation o f CD4(+) T cells and that buspirone induced expression of IL-2 mRNA.