Interactions between cytokines and growth hormone for resistance to experimental Toxoplasma gondii infection

Cytokine-activated human vein endothelial cells (HUVEC) may play an importa nt role in resistance to Toxoplasma gondii infection. In this study, it was investigated the role of rTNF-alpha and GH in the induction of antitoxopla smal activities in HUVEC. Go-treatment of HUVEC with rTNF-alpha plus GH ind uced both toxoplasmastatic activity and the intracellular killing of T. gon dii (p <0.01 each vs untreated cells). Thus, these functions were inhibited by both neutralizing antibodies to IL-6 and GM-CSF (but not to IL-3) sugge sting that these cytokines participate in the inhibitory process. Consisten t with this hypothesis, the treatment of HUVEC with rIL-6 or rGM-CSF in the presence of rTNF-alpha, limited T. gondii multiplication in a dose-depende nt manner (p <0.01 each vs untreated cells). In order to elucidate the inhi bitory mechanism of HUVEC, it was assessed by L-arginine analogs (e.g., N-G -monomethyl-arginine) whether NO2- molecules originating from HUVEC were di rectly or indirectly involved in the rTNF-alpha/GH-dependent induction of t oxoplasmastatic activity. A good correlation was found between toxoplasmast atic activity and NO2- release during the activation phase, before infectio n of the HUVEC with T, gondii, but no correlation was found between the par asitostatic activity and NO2- release during the infection phase. These dat a indicate that NO2- itself does not directly affect toxoplasmastatic activ ity. Besides, the reduction of intracellular killing by monoclonal antibodi es to ICAM-1 suggest that this adhesin plays a role in controlling T. gondi i entry into cells.