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

To evaluate the prophylactic properties of integrin CD18-betaA peptide in a murine model of abdominal polymicrobial peritonitis and sepsis.

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-betaA 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)-alpha 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.

Intraperitoneal injection of CD18-betaA peptide significantly suppressed circulating endotoxin activity (P < 0.01) at 24 h, as well as serum levels of TNF-alpha (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-betaA 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-betaA peptide collectively protected septic mice against lethality (P < 0.01).

CD18-betaA peptide is a potent endotoxin antagonist that can protect surgical patients against sepsis-associated lethality.