['\u2003Sepsis 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-36α (IL-36α) in host response during sepsis remains unknown.', '\u2003An experimental sepsis model of cecal ligation and puncture (CLP) was established to investigate the effects of IL-36α on host response to sepsis.', '\u2003IL-36α production was significantly up-regulated during sepsis. IL-36α treatment reduced mortality in mice with severe sepsis by CLP. IL-36α-treated mice developed 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-36α led to increased mortality in mice with nonsevere sepsis. Furthermore, we found that IL-36α enhanced bacterial phagocytosis and killing by macrophages, thereby allowing local and systemic bacterial clearance. Importantly, macrophage depletion before the onset of sepsis eliminated IL-36α-mediated protection against sepsis.'] Does interleukin-36α attenuate sepsis by enhancing antibacterial functions of macrophages?