Interleukin 36α Attenuates Sepsis by Enhancing Antibacterial Functions of Macrophages.

Background. Sepsis is newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality rate and limited effective treatments. The role of interleukin 36 alpha (IL-36 alpha) in host response during sepsis remains unknown. Methods. An experimental sepsis model of cecal ligation and puncture was established to investigate the effects of IL-36 alpha on host response to sepsis. Results. IL-36 alpha production was significantly up-regulated during sepsis. IL-36 alpha treatment reduced the mortality rate in mice with severe sepsis by cecal ligation and puncture. IL-36 alpha-treated mice had more efficient bacterial clearance, inhibited tissue inflammation, improved organ injury, and reduced immune cell apoptosis. The therapeutic implication of these observations was also highlighted by the finding that specific blockade of IL-36 alpha led to an increased mortality rate in mice with nonsevere sepsis. Furthermore, we found that IL-36 alpha enhanced bacterial phagocytosis and killing by macrophages, thereby allowing local and systemic bacterial clearance. Importantly, macrophage depletion before the onset of sepsis eliminated IL-36 alpha-mediated protection against sepsis. Conclusions. Our results demonstrate that IL-36 alpha plays an important role in the host defense response to sepsis and suggest a potential therapeutic role for IL-36 alpha in sepsis.