Release of endogenous heat shock protein 72 on the survival of sepsis in rats

BackgroundThis study was undertaken to clarify the role of extracellular heat shock protein 72 on the survival of sepsis and to determine possible factor(s) that may be responsible for it.Materials and methodsSepsis was induced by cecal ligation and puncture. Changes in serum levels of heat shock protein (Hsp72) and cytokines were determined during sepsis, and the results were correlated with the survival. Effects of heat pretreatment on Hsp72 expression in septic rat leukocytes and those of septic rat serum, lipopolysaccharide (LPS), and certain cytokines on the release of Hsp72 in macrophage NR8383 cells were determined.ResultsCirculating Hsp72 levels were increased during the progress of sepsis (0, 5.5, 6.5, 10, and 6.5 ng/mL at 0, 3, 6, 9, and 18 h after cecal ligation and puncture, respectively) and the increases were correlated positively with survival rates. LPS triggered the release of Hsp72 in heat pretreated animals. Heat pretreatment increased Hsp72 expression in nonsepsis (+535%, P < 0.01) and sepsis (+116%, P<0.01%) rat leukocytes. Incubation of sepsis rat serum with NR8383 cells increased levels of extracellular heat shock protein 72 in cultured medium. Cytokine profiling revealed that among the 19 cytokines screened, four of them were increased as follows: cytokine-induced neutrophil chemoattractant 3 (+211.3%, P < 0.05), interleukin 10 (+147%, P < 0.05), MCP-1 (+49.6%, P < 0.05), and tumor necrosis factor alpha (+51.8%, P < 0.05). MCP-1 and LPS were capable of releasing Hsp72 from NR8383 cells.ConclusionsThese results demonstrate that the increases in the levels of circulating Hsp72 had a beneficial effect in improving animal survival during the progress of sepsis. The increases in circulating Hsp72 may be mediated via MCP-1 and/or LPS.