Research Of Interleukin-34 Ameliorates Survival And Bacterial Clearance In Sepsis

Background:Sepsis is a devastating condition with a high mortality rate and limited treatments.Sepsis is characterized by a failed host immune response to contain the infection,resulting in organ dysfunction.Interleukin-34 is new cytokine involved in infection and immunity.Whether interleukin-34 is beneficial or deleterious to sepsis and the underlying mechanisms remains unknown.Methods : Interleukin-34 concentrations were measured in human sepsis patients and healthy individuals.A murine model of cecal ligation and puncture–induced sepsis was established to investigate the effects of interleukin-34 administration on survival,bacterial burden,organ injury,and inflammatory response.Results : Interleukin-34 levels were significantly elevated in human sepsis and cecal ligation and puncture–induced experimental sepsis.Interleukin-34 administration improved survival and bacterial clearance,although suppressed vascular leakage and organ injury after cecal ligation and puncture–induced polymicrobial sepsis.Neutralization of interleukin-34 increased mortality rate and decreased bacterial clearance in septic mice.An increased neutrophil and macrophage influx were developed in interleukin-34–treated mice at the site of infection,accompanied by elevated production of neutrophil chemokine CXCL1 andmacrophage chemokine CCL2 in the peritoneal cavity.Depletion of neutrophils or macrophages reversed interleukin-34–mediated protection against polymicrobial sepsis.Conclusions: We reported for the first time a potential therapeutic role for interleukin-34 in sepsis and suggested that interleukin-34 is a novel target for the development of therapeutic agents against sepsis.