Prophylactic uses of integrin CD18-βA peptide in a murine polymicrobial peritonitis model

AIM:To evaluate the prophylactic properties of integrin CD18-βA peptide in a murine model of abdominal polymicrobial peritonitis and sepsis.METHODS:Bacterial sepsis was induced in Institute of Cancer Research(ICR) mice by cecal ligation and puncture(CLP) surgery.Inflicted mice were then injected with either sterile saline or CD18-βA peptide intraperitoneally at 2 h after surgery,and were sacrificed at 12 and 24 h after surgery.Blood samples were immediately collected,and analyzed for endotoxin activity and tumor necrosis factor(TNF)-α and interleukin(IL)-6.Lungs and liver were studied for CD45+ leukocyte and CD3 mRNA content.Pulmonary expression of intercellular adhesion molecule(ICAM)-1,vascular cell adhesion molecule(VCAM) and E-selectin was also determined.RESULTS:Intraperitoneal injection of CD18-βA peptide significantly suppressed circulating endotoxin activity(P<0.01) at 24 h,as well as serum levels of TNF-α(P<0.05 at 12 and 24 h) and IL-6(P<0.01 at 12 h,P<0.05 at 24 h) in CLP-inflicted mice.CD18-βA peptide also abrogated leukocyte infiltration into liver and lungs as unveiled by reduced CD45+ leukocyte and CD3 mRNA contents.Furthermore,the peptide significantly reduced pulmonary expression of VCAM(P<0.01 at 12 h,P<0.001 at 24 h),E-selectin(P<0.01 at 12 and 24 h),and ICAM-1(P<0.01 at 12 h,P<0.001 at 24 h).These actions of CD18-βA peptide collectively protected septic mice against lethality(P<0.01).CONCLUSION:CD18-βA peptide is a potent endotoxin antagonist that can protect surgical patients against sepsis-associated lethality.