Interleukin‐17, oxidative stress, and inflammation: role of melatonin during Trypanosoma cruzi infection

Abstract

Although the exact etiology of Chagas' disease remains unknown, the inflammatory process and oxidative stress are believed to be the main contributors to the dysfunction and pathogenesis during chronic Trypanosoma cruzi infection. Our hypothesis is that melatonin administered for 2 months daily could modulate the oxidative stress and the inflammatory response during the chronic infection. Flow cytometric analysis of macrophages and antigen-presenting cells (APC), expression of RT1B as well as LFA-1 and MCP-1 in CD4(+) and CD8(+) T cells and levels of interleukin-17A were assessed. The oxidative stress was evaluated through lipid peroxidation (LPO) analysis on the plasma of thiobarbituric acid-reactive substances (TBARS) and nitric oxide production. Decreased concentrations of nitrite and TBARS were found in infected and melatonin-treated animals, as well as a rising trend in the production of IL-17A as compared to infected and untreated counterparts. A significant decrease was found in the percentages of CD4(+) and CD8(+) T lymphocytes MCP-1 producers for infected and melatonin-treated rats. Reduced percentage of CD8(+) T cells producing LFA-1 was observed in control and melatonin-treated animals as compared to untreated rats. The cellular response of peritoneal APC cells and macrophages significantly dropped in infected and treated animals. As an endpoint, the use of antioxidant compounds such as melatonin emerges as a new and promising approach to control the oxidative stress during the chronic Chagas' disease partially mediated through the abrogation of LPO and the prevention of the inflammatory response and can be used for further investigation on treatment trials for other infectious diseases.

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

“…Our group and others have demonstrated the beneficial effect of melatonin administration upon the acute upon T. cruzi infection on animal models, through reduction in blood parasites as well as tissue amastigote burdens, and inflammatory infiltrate The actions of melatonin were also observed by Gazarini et al . with a significant impact on the development of the parasite Plasmodium chabaudi in mice triggering a complex signaling pathway.…”

“…Melatonin was administered at the same time each day. Treatment started at the same day of the infectious inocule and then kept on every day until the end of the experiment (9 days after infection) …”

Melatonin in macrophage biology: Current understanding and future perspectives

“…Melatonin treatment shows various beneficial effects in T cruzi ‐infected rats, including alleviation of nitroxidative stress (as evident by reduced lipid peroxidation and nitrite produced by cultured peritoneal macrophages). Moreover, numbers of peritoneal macrophages were decreased, however, to levels much below those of uninfected controls . The protective role of melatonin is not restricted to macrophages, but has also to be seen in the context of effects on other immune cells, such as T lymphocytes and thymocytes …”

“…Trypanosoma cruzi infection is the cause of Chagas’ disease. Increased oxidative stress and intense inflammatory responses are typical for the chronic T cruzi infection and critical for its chronic progression . Melatonin treatment shows various beneficial effects in T cruzi ‐infected rats, including alleviation of nitroxidative stress (as evident by reduced lipid peroxidation and nitrite produced by cultured peritoneal macrophages).…”

Melatonin signaling in T cells: Functions and applications

“…The regulation of melatonin in other T‐cell‐based diseases requires further investigation. Indeed, results of recent studies showed that melatonin is highly effective in regulating the pathogenesis of cancers and infections through the melatonin‐T‐cell response axis …”