Inducible cyclooxygenase released prostaglandin mediates immunosuppression in acute phase of experimental Trypanosoma cruzi infection.
We investigated the possible role of prostaglandins produced by COX-2 in the immunosuppression observed during Trypanosoma cruzi infection. Con-A-stimulated splenocytes isolated from mice on days 5, 10, and 15 of infection released large amounts of PGE2 and this release was inhibited by the treatment of animals with sodium salicylate or meloxicam. The treatment of the animals with these drugs enhanced the release of IL-2 by splenocytes from T. cruzi-infected animals and significantly reduced the blood parasitemia and delayed the mortality of the infected mice. Furthermore, the release of TNF-alpha, IFN-gamma, IL-4, and IL-10 by Con-A-stimulated splenocytes obtained from infected mice on days 5, 10, and 15 of the infection was significantly inhibited by treatment of the animals with salicylate or meloxicam. In conclusion, the results suggest that the prostaglandins produced mainly by COX-2 mediate the immunosuppression observed in the acute phase of T. cruzi infection.
Michelin
M A
MA
Department of Biological Sciences, Immunology, Federal School of Medicine, Uberaba, MG, Brazil. michelinimuno@dcb.fmtm.br
Silva
J S
JS
Cunha
F Q C
FQ
D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology*; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D000077239:Meloxicam; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D012980:Sodium Salicylate / Q000494:pharmacology / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013843:Thiazines / Q000494:pharmacology / Q000627:therapeutic use; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D013843:Thiazines; D013844:Thiazoles; D003208:Concanavalin A; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D000077239:Meloxicam; D012980:Sodium Salicylate