Effects of cytokines and prolactin on the replication of Toxoplasma gondiiin murine microglia

In the central nervous system, cytokine-activated microglia play a crucial role in host defence against Toxoplasma gondii infections. In this study, t he effect of recombinant tumor necrosis factor (rTNF)-alpha and prolactin ( PRL) on T.gondii infection In microglia was examined. Pretreatment of micro glia with rTNF-alpha and PRL induced toxoplasmastatic activity, the intrace llular killing of T. gondii and the release of kinterleukin (IL)-1 beta IL- 3 and IL-6: 50% of the intracellular killing was abrogated by anti-ICAM-1 m onoclonal antibodies, whereas more than 54 or 87% of toxoplasmastatic activ ity was reversed by wanti-IL-3 or IL-6 monoclonal antibodies. In addition, the treatment of microglia with either rIL-3 or rIL-6,in the absence of pre sence of rTNF-alpha significantly limited T. gorzdii replication, Inasmuch as either NMA or S-M-ITU affected cytokine-activated toxoplasmastatic activ ity during the infection phase, the NO-dependent pathway itself appears not to be directly involved in the parasitostatic activity. These findings sug gest that TNF-a and PRE up-regulate the expression of ICAM-1 and the produc tion of endogenous IL-6 and IL-3 by microglia, which could induce antiparas itic functions against I: gondii infection in the brain.