Melatonin: Antioxidant and modulatory properties in age-related changes during Trypanosoma cruzi infection.

The purpose of this study was to investigate the effects of melatonin on selected biomarkers of innate and humoral immune response as well as the antioxidant/oxidant status (superoxide dismutase-SOD and reduced glutathione levels (GSH) to understand whether age-related changes would influence the development of acute Trypanosoma cruzi (T. cruzi) infection. Young- (5 weeks) and middle-aged (18 months) Wistar rats were orally treated with melatonin (gavage) (05 mg/kg/day), 9 days after infection. A significant increase in both SOD activity and GSH levels was found in plasma from all middle-aged melatonin-treated animals. Melatonin triggered enhanced expression of major histocompatibility class II (MHC-II) antigens on antigen-presenting cell (APC) and peritoneal macrophages in all treated animals. High levels of CD4+ CD28-negative T cells (*P<.05) were detected in middle-aged control animals. Melatonin induced a significant reduction (***P<.001) in CD28-negative in CD4+ and CD8+ T cells in middle-aged control animals. Contrarily, the same group displayed upregulated CD4+ CD28+ T and CD8+ CD28+ T cells. Melatonin also triggered an upregulation of CD80 and CD86 expression in all young-treated groups. Significant percentages of B and spleen dendritic cells in middle-aged infected and treated animals were observed. Our data reveal new features of melatonin action in inhibiting membrane lipid peroxidation, through the reduction in 8-isoprostane, upregulating the antioxidant defenses and triggering an effective balance in the antioxidant/oxidant status during acute infection. The ability of melatonin to counteract the immune alterations induced by aging added further support to its use as a potential therapeutic target not only for T. cruzi infection but also for other immunocompromised states.

Interleukin-1 receptor antagonist decreases cerebrospinal fluid nitric oxide levels and increases vasopressin secretion in the late phase of sepsis in rats.

The aim of this study was to analyze the effect of IL-1ra (an Interleukin-1 receptor antagonist) on sepsis-induced alterations in vasopressin (AVP) and nitric oxide (NO) levels. In addition, IL-1ra effect on the hypothalamic nitric oxide synthase (NOS) activities and survival rate was also analyzed. After Wistar rats were intracerebroventricular injected with IL-1ra (9 pmol) or vehicle (PBS 0.01 M), sepsis was induced by cecal-ligation and puncture (CLP). Blood, CSF, and hypothalamic samples were collected from different groups of rats (n = 8/group) after 4, 6, and 24 h. AVP and NO levels were greatly increased in CLP. Both total NOS and inducible NOS (iNOS) activities were also greatly increased in CLP rats. These changes in AVP, NO, and NOS were not observed in sham-operated control rats. IL-1ra administration did not alter plasma AVP levels after 4 and 6 h as compared to vehicle in CLP animals but after 24 h were significantly (P < 0.01) higher in IL-1ra-treated animals. IL-1ra administration significantly (P < 0.01) decreased NO concentration in CSF but not in plasma. Both total NOS and iNOS activities were also significantly decreased by IL-1ra at 24 h in CLP animals. Moreover, the 24 h survival rate of IL-1ra-treated rats increased by 38 % in comparison to vehicle administered animals. The central administration of IL-1ra increased AVP secretion in the late phase of sepsis which was beneficial for survival. We believe that one of the mechanisms for this effect of IL-1ra is through reduction of NO concentration in CSF and hence lower hypothalamic iNOS activities in the septic rats.