Gentamicin promoted the production of CD4+CD25+ Tregs via the STAT5 signaling pathway in mice sepsis

Increasing studies have reported that gentamicin (GNT) plays an essential role in sepsis; however, its underlying mechanism is still unclear. In this study, we investigated the mechanism of GNT in sepsis. We observed that GNT enhanced survival and alleviated inflammatory injuries of the lungs, liver, kidneys, and intestines in mice with sepsis. Furthermore, regulatory T cells (Tregs) showed enhanced inhibitory function, and pro-inflammatory cytokines IL-1[beta], TNF-[alpha], and IL-2 and anti-inflammatory cytokine IL-10 showed decreased and increased peritoneal fluid levels, respectively, after treatment with GNT. GNT showed enhanced phosphorylation of signal transducer and activator of transcription 5 (p-STAT5) in Tregs in vivo and in vitro. The STAT5 inhibitor restrained the increased functional changes of Tregs and reduced inflammatory responses induced by GNT in vitro. Moreover, the STAT5 inhibitor reversed GNT-mediated impacts on survival and inflammation, and the percentage, apoptosis, and phenotypic and functional changes of Tregs in neonatal sepsis. Our study revealed that GNT regulates the function of Tregs via the STAT5 signaling pathway, alleviating inflammatory injuries, and provides novel evidence in the treatment of neonatal sepsis.