ABSTRACT
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.
Subject(s)
Chagas Disease/immunology , Cytokines/physiology , Dinoprostone/physiology , Immune Tolerance/physiology , Prostaglandin-Endoperoxide Synthases/metabolism , Acute Disease , Animals , Cells, Cultured , Chagas Disease/drug therapy , Chagas Disease/metabolism , Concanavalin A/pharmacology , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/pharmacology , Cyclooxygenase Inhibitors/therapeutic use , Cytokines/biosynthesis , Dinoprostone/biosynthesis , Immune Tolerance/drug effects , Lymphocyte Activation/drug effects , Male , Meloxicam , Mice , Mice, Inbred BALB C , Parasitemia/drug therapy , Parasitemia/immunology , Parasitemia/metabolism , Prostaglandin-Endoperoxide Synthases/drug effects , Sodium Salicylate/pharmacology , Sodium Salicylate/therapeutic use , Spleen/cytology , Spleen/drug effects , Spleen/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Thiazines/pharmacology , Thiazines/therapeutic use , Thiazoles/pharmacology , Thiazoles/therapeutic useABSTRACT
Several lines of evidence in experimental animals indicate that the kinin system may participate in the pathogenesis of envenomation by the Tityus serrulatus (Ts) scorpion sting, but there are no studies in humans with regard to this system. In this study, we evaluated the plasma levels of high-molecular (HKg) and low-molecular (LKg) weight kininogens (detected by ELISA), the activities of plasma or tissue kallikreins and kininase II (enzymatic action upon selective substrates), and the Ts plasma venom levels (ELISA). A total of 27 patients (12 males) aged 12-72 were evaluated immediately at hospital admittance. According to the severity of envenomation, patients were classified as mild (n = 15), moderate (n = 8), and severe cases (n = 4). Controls were paired for age and sex. Plasma venom levels were associated with the severity of envenomation. Severe cases presented lower levels of LKg in relation to mild and controls. Inverse correlations were seen between LKg levels and the venom concentration. The results of this study suggested that the kinin system may participate in the pathogenesis of human Ts envenomation and knowledge about this system may be useful to develop new strategies to reduce the damage caused by scorpion envenomation.
Subject(s)
Blood Glucose , Kallikreins/metabolism , Kinins/drug effects , Scorpion Venoms/adverse effects , Spider Bites/blood , Adolescent , Adult , Aged , Enzyme-Linked Immunosorbent Assay , Female , Humans , Kininogens/blood , Kinins/blood , Male , Middle Aged , Scorpion Venoms/blood , Severity of Illness Index , Spider Bites/classificationABSTRACT
Scorpion envenomation is a common medical problem in many countries and an important cause of morbidity and mortality, especially among children. The plasma levels of pro-inflammatory (IL-1beta, IL-6, IL-8 and TNF-alpha) and anti-inflammatory (IL-10) cytokines were measured in individuals stung by Tityus serrulatus (Ts) scorpions. According to clinical manifestations patients were classified, as defined by the Brazilian Ministry of Health, as having mild (n=15, mean age=42.2 years), moderate (n=8, mean age=26 years) or severe (n=4, mean age=14 years) envenomation. Blood samples were taken immediately (T1) and 6h (T2) after admission to the hospital. Eighteen age-matched healthy volunteers were used as control. TNF-alpha, IL-1beta, IL-6 and IL-8 levels were significantly increased in moderate and severe cases and the levels of these cytokines were positively correlated with the severity of envenomation, as evaluated by clinical profile and plasma venom concentration. IL-10 levels were increased in severe and moderate cases and reduced in mild cases. The results reported in the present study suggest that the physiopathological manifestation of Ts envenomation may be mediated, at least in part, by cytokines, and that the early treatment after scorpion sting with drugs that inhibit cytokine production, such as glucocorticoids, may have a potential beneficial effect, ameliorating the severity of the clinical manifestations observed, particularly in severe and moderate cases.
