IN-VITRO AND IN-VIVO IMMUNOMODULATORY EFFECTS OF ANTIPNEUMOCYSTIS CARINII DRUGS

The anti-Pneumocystis carinii drug effects on mitogen-, antigen-, and interleukin-2-induced proliferative responses and on natural killer (N K) cell-mediated activity were analyzed in vivo (rats) and in vitro (n ormal human peripheral blood mononuclear cells). Splenocytes derived f rom in vivo piritrexim- and clindamycin-treated rats showed a signific ant inhibition of mitogen-induced proliferative responses. In vitro ex posure to clindamycin, piritrexim, and pyrimethamine caused an inhibit ion of human T lymphocyte proliferation in response to mitogen, antige n, and interleukin-2 stimulation. Rat NK cell-mediated cytotoxic activ ity was not affected by the drugs, and human NK cell activity was redu ced only at the highest concentration (10 mu g/ml) of the drugs. The p otential immunotoxicity of the long-term administration of these agent s in humans needs further investigation.