mobic and Chagas-Disease

The aim of this study was to evaluate a possible synergism between melatonin and meloxicam in up-regulating the immune response in male Wistar rats infected with Trypanosoma cruzi during immunosuppression phenomenon, which characterizes the acute phase of the Chagas' disease. Male Wistar rats were infected with the Y strain of T. cruzi. Experiments were performed on 7, 14 and 21 days post-infection. Several immunological parameters were evaluated including gamma-interferon (IFN-gamma), interleukin-2 (IL-2), nitric oxide (NO) and prostaglandin E(2) (PGE(2)). The combined treatment with melatonin and meloxicam significantly enhanced the release of IL-2 and INF-gamma into animals' serum, when compared with the infected control groups during the course of infection. Furthermore, the blockade of PGE(2) synthesis and the increased release of NO by macrophage cells from T. cruzi-infected animals contributed to regulate the production of Th1 subset cytokines significantly reducing the parasitaemia in animals treated with the combination of both substances. Therefore, our results suggest that the association of melatonin and meloxicam was more effective in protecting animals against the harmful actions of T. cruzi infection as compared with the treatments of meloxicam or melatonin alone.

Topics: Animals; Chagas Disease; Dinoprostone; Drug Synergism; Immunologic Factors; Interferon-gamma; Interleukin-2; Macrophages; Male; Melatonin; Meloxicam; Nitric Oxide; Rats; Rats, Wistar; Thiazines; Thiazoles; Trypanosoma cruzi

Chagas disease is characterized by cardiac lesions and a high level of PGE2. Our objective was to investigate the role of PGE2 in cardiac lesions. BALB/c mice were infected with Trypanosoma cruzi (1x10(3) trypomastigote forms) and were treated daily with PBS, meloxicam (0.5 mg/kg) or etoricoxib (0.6 mg/kg). The animals were sacrificed on the 21st day of infection and we collected the cardiac tissue and spleen cells for tissue culture. We observed that treatment with COX-2 inhibitors was able to decrease synthesis of PGE2 by spleen cells. This reduction was accompanied by reduction of the inflammatory infiltrate, parasite nets, cardiac fibrosis and fewer COX-2 positive cells in cardiac tissue obtained from these animals. In conclusion, treatment with COX-2 inhibitors, and consequent inhibition of PGE2 synthesis, was able to reduce the cardiac damage observed during the acute phase of experimental Chagas disease, thus demonstrating the involvement of this mediator in the cardiac lesion.

Topics: Acute Disease; Animals; Cells, Cultured; Chagas Disease; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dinoprostone; Etoricoxib; Fibrosis; Male; Meloxicam; Mice; Mice, Inbred BALB C; Myocardium; Parasitemia; Prostaglandins; Pyridines; Spleen; Sulfones; Thiazines; Thiazoles; Trypanosoma cruzi

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.

Topics: Acute Disease; Animals; Cells, Cultured; Chagas Disease; Concanavalin A; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Cytokines; Dinoprostone; Immune Tolerance; Lymphocyte Activation; Male; Meloxicam; Mice; Mice, Inbred BALB C; Parasitemia; Prostaglandin-Endoperoxide Synthases; Sodium Salicylate; Spleen; T-Lymphocytes; Thiazines; Thiazoles