부산대학교 도서관

Purpose Animal milk fat globule-EGF factor 8 (MFG-E8) has been shown to be beneficial in attenuating the inflammatory response in sepsis. In this study, we examined the effect of recombinant human MFG-E8 (rhMFG-E8) in an animal model of sepsis in an effort to develop it as a potential therapy against sepsis in humans. Methods Rats were subjected to sepsis by cecal ligation and puncture (CLP), and at 5 h post-CLP, they were given different doses of rhMFG-E8 (20, 40, 80, 160 [mu]g/kg BW) in normal saline. At 20 h post-CLP, samples were collected for further analysis. A 10-day survival study was also performed. Results At 20 h after CLP, organ injury indicators, serum IL-6 and TNF-[alpha], and plasma HMGB-1 levels were significantly increased as compared to sham-operated animals. Treatment with 20 [mu]g/kg rhMFG-E8 significantly reduced these levels. With higher doses, further reductions in AST and ALT (59-62%), creatinine (65-68%), and lactate (46-57%), and serum IL-6 and TNF-[alpha] were obtained. The 160 [mu]g/kg dose produced the greatest reduction in serum TNF-[alpha]. With treatment with 20 [mu]g/kg rhMFG-E8, HMGB-1 levels decreased by 80%, returning back to sham values. In a 10-day survival study, vehicle-treated animals produced a 36% survival rate, while rhMFG-E8 significantly improved the survival rate to 68-72%. Treatment with increasing doses of rhMFG-E8 significantly reduced the number of apoptotic cells detected and markedly attenuated the tissue damages observed in the lungs. Conclusions These data suggest that recombinant human MFG-E8 is beneficial in ameliorating sepsis in an animal model of sepsis.
Author(s): Kavin G. Shah [sup.1], Rongqian Wu [sup.1] [sup.2], Asha Jacob [sup.1] [sup.2], Ernesto P. Molmenti [sup.1], Jeffrey Nicastro [sup.1], Gene F. Coppa [sup.1], Ping Wang [sup.1] [sup.2] Author Affiliations: [...]