Effect of Ethyl Pyruvate on Physical and Immunological Barriers of the Small Intestine in a Rat Model of Sepsis

Background: Physical and immunologic barriers of the small intestine play an important role in development and treatment of sepsis, so a rat model of sepsis was used to investigate the effect of ethyl pyruvate (EP) on the barriers. Methods: Male Wistar rats were divided into sham operated, cecal ligation and puncture, and EP groups. Survival and bacterial translocation were measured in response to EP administration. Physical barrier (including mitochondria of enterocyte, tight junction, micro-villi, and the grade of small intestinal mucosa damage) and immunologic barrier (including distribution of T-cell subgroups in small intestinal villi, proportion of T-cell subgroups in mesenteric lymph nodes and spleens, proliferation and cytokines release of splenocytes) were determined by electron and light microscopy, immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Results: Sepsis induced morphologic alteration and immunosuppression in the small intestine. EP administration can prevent these changes, especially immunologic change. Distribution of CD4+ T cells in villi, proportions of CD4+ T cells in mesenteric lymph nodes and spleens, and proliferative capacity of splenocytes were increased in rats treated with EP. Interferon-gamma and Interleukin-4 release were also modulated. Moreover, EP improved survival from 37.1% to 57.1% and reduced bacterial translocation. Conclusions: EP administration ameliorated physical and immunologic barriers dysfunction of small intestine in a rat model of sepsis. EP may be used to treat sepsis as an immunologic modulator.