Therapeutic Targeting of Apoptosis Inhibitor of Macrophage/CD5L in Sepsis

The factors involved in disturbing host homeostasis during sepsis are largely unknown. We sought to determine the immunopathological role of apoptosis inhibitor of macrophage (AIM)/CD5L in sepsis. Here, we show that blockade of AIM led to significantly increased survival after experimental sepsis, and it decreased local and systemic inflammation, reduced tissue injury, and inhibited bacterial dissemination in the blood, in particular at later time points. Supplementation of recombinant AIM in sepsis resulted in increased tissue injury, amplified inflammation, increased bacteremia, and worsened mortality. Interestingly, the most important difference in the production of cytokines and chemokines after in vivo AIM blockade or AIM administration during sepsis was IL-10. In vitro, AIM enhanced IL-10 production from macrophages, neutrophils, or lymphocytes. In vivo, the beneficial effects of AIM blockade and the detrimental effects of AIM addition on experimental sepsis were ablated by treatment with recombinant IL-10 and neutralizing anti-IL-10 antibodies, respectively. This study is the first to identify AIM as an important mediator in disturbing host homeostasis in sepsis.