Immunomodulation of Ethyl pyruvate on gestational diabetes mellitus in Mice; The impact on Th17/Treg balance

Abstract

Gestational diabetes mellitus (GDM) is recognized as one of the most common diseases among pregnant women and inflammatory responses can be a major reason for its induction and development. T helper 17 (Th17)/regulatory T cells (Tregs) imbalance resulting in the increased levels of pro-inflammatory and decreased levels of anti-inflammatory cytokines has been showed as major mechanisms involved in the pathogenesis of GDM. There are various treatment options, but none of them are completely therapeutic. Ethyl pyruvate (EP) is a stable derivate of pyruvate that showed anti-oxidant and anti-inflammatory properties in an in-vivo and in-vitro models. To examine the therapeutic efficacy of EP in GDM, mice were mated and EP (100 mg/kg) was administered intraperitoneally to C57BL/6 mice. EP-treated mice exhibited improved symptoms of GDM by decreased blood glucose levels and body-weight and increased insulin levels and insulin sensitivity. Furthermore, EP could significantly attenuate the impairments to offspring, including birth size and birth weight. The inflammatory responses were also decreased by EP through regulating the production of Th17-related cytokines, such as interleukin (IL)- 17 and IL-21. The levels of other inflammatory cytokines were also inhibited, including IL-1β, IL-6, and tumor necrosis factor (TNF)-α. In addition, it was found that EP increased the population of Tregs and Treg-related cytokines, IL-10 and transforming Growth Factor-β TGF-β, in GDM mice. In conclusion, EP could modulate GDM in mice and might be a potential therapeutic strategy candidate for the treatment of patients with GDM.

Keywords: Ethyl pyruvate; Gestational diabetes mellitus (GDM); Inflammation; Regulatory T cell (Treg); T helper (Th) 17.