In vitro hydroxyurea decreases th1 cell-mediated immunity

Hydroxyurea (HU) is used in the treatment of hematologic disorders and is s ometimes added to antiretroviral combination therapy to potentiate human im munodeficiency virus (HIV) suppression. However, HU has toxic effects on ra pidly dividing cells, including the effecters of the immune response. To de termine whether HU affects specific T-cell responses, we measured lymphocyt e proliferation and cytokine production in response to microbial antigen an d mitogen stimulation in the presence of added HU (10 to 1,000 muM). HU tre atment of peripheral blood mononuclear cells obtained from HIV-infected pat ients and uninfected controls decreased lymphocyte proliferation and gamma interferon production compared with untreated cells. Interleukin-2 (IL-2) a nd IL-10 production was not affected by HU, The HU-mediated decrease of lym phocyte proliferation was similar in peripheral blood mononuclear cells fro m HIV-infected patients and from uninfected controls. The inhibitory effect of HU required continuous exposure to the drug and could be reverted by wa shing the drug out of the culture environment. These findings suggest that HU-containing therapeutic regimens might decrease Th1-cell-mediated immune responses in vivo.