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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.
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- [beta] A 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, well well as serum levels of TNF-α (P <0.05 at 12 and 24 h) and IL-6 12 h, P <0.05 at 24 h) in C LP-inflicted mice. CD18-βA peptide also abrogated leukocyte infiltration into liver and lungs as unveiled by reduced CD45 + leukocyte and CD3 mRNA contents. Frthermore, the peptide significantly reduced pulmonary expression of VCAM (P <0.01 at 12 h, P <0.001 at (P <0.001 at 24 h), E-selectin (P <0.01 at 12 and 24 h), and ICAM-1 lethality (P <0.01) .CONCLUSION: CD18-βA peptide is a potent endotoxin antagonist that can protect surgical patients against sepsis-associated lethality.