Ghrelin Protects against Experimental Sepsis by Inhibiting High-Mobility Group Box 1 Release and by Killing Bacteria

摘要: Sepsis, a life-threatening complication of infections and the most common cause death in intensive care units, is characterized by hyperactive out-of-balance network endogenous proinflammatory cytokines. None current therapies are entirely effective, illustrating need for novel therapeutic approaches. Ghrelin (GHR) an orexigenic peptide that has emerged as potential anti-inflammatory factor. In this study, we show delayed administration GHR protects against mortality various models established endotoxemia sepsis. The effect mainly mediated decreasing secretion high mobility box 1 (HMGB1), DNA-binding factor acts late inflammatory critical sepsis progression. Macrophages seem to be major cell targets inhibition HMGB1 secretion, which blocked its cytoplasmic translocation. Interestingly, also report shows potent antibacterial activity septic mice vitro. Remarkably, reduces severity experimental arthritis release serum. Therefore, regulating crucial processes sepsis, such production early mediators macrophages microbial load, represents feasible agent disease other disorders.