Interactions between cytokines and growth hormone for resistance to experimental.
Cytokine-activated human vein endothelial cells (HUVEC) may play an important role in resistance to Toxoplasma gondii infection. In this study, it was investigated the role of rTNF-alpha and GH in the induction of antitoxoplasmal activities in HUVEC. Co-treatment of HUVEC with rTNF-alpha plus GH induced both toxoplasmastatic activity and the intracellular killing of T. gondii (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) suggesting that these cytokines participate in the inhibitory process. Consistent 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-dependent manner (p <0.01 each vs untreated cells). In order to elucidate the inhibitory mechanism of HUVEC, it was assessed by L-arginine analogs (e.g., NG-monomethyl-arginine) whether NO2 molecules originating from HUVEC were directly or indirectly involved in the rTNF-alpha/GH-dependent induction of toxoplasmastatic activity. A good correlation was found between toxoplasmastatic activity and NO2 release during the activation phase, before infection of the HUVEC with T. gondii, but no correlation was found between the parasitostatic activity and NO2 release during the infection phase. These data indicate that NO2- itself does not directly affect toxoplasmastatic activity. Besides, the reduction of intracellular killing by monoclonal antibodies to ICAM-1 suggest that this adhesin plays a role in controlling T. gondii entry into cells.
Benedetto
N
N
Istituto di Microbiologia Seconda Università degli Studi di Napoli, Italy.
Folgore
A
A
Gorga
F
F
Finamore
E
E
Rao
M
M
Galdiero
F
F
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000166:cytology / Q000469:parasitology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007378:Interleukins / Q000494:pharmacology; D009500:Neutralization Tests; D009569:Nitric Oxide / Q000096:biosynthesis; D014122:Toxoplasma / Q000187:drug effects*; D014123:Toxoplasmosis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013006:Growth Hormone