PROTECTIVE EFFECTS OF A NOVEL 32-AMINO ACID C-TERMINAL FRAGMENT OF CAP18 IN ENDOTOXEMIC PIGS

Background. Cationic antimicrobial protein of 18 kd (CAP18) is a neutrophil-derived peptide that binds lipopolysaccharide (LPS) with high affinity. We hypothesized that CAP18(106-137), a novel synthetic 32-amino acid C-terminal fragment of CAP18, would neutralize the physiologic derangements induced by LPS in anesthetized swine. Methods. Pigs were randomly allocated into three groups. Those in the LPS group (n = 6) were infused with LPS (3 mu g/kg/hr for 3 hours). Pigs in the LPS/CAP18 group (n = 6) were challenged with LPS (3 mu g/kg/hr for 4 hours) and also treated with CAP18(106-137) (4 mg/kg/hr for 4 hours). Pigs in the RL group (n = 4) received neither LPS nor CAP18(106-137). Results. Treatment with CAP18(106-137) blocked LPS-induced increases in plasma levels of 6-keto-prostaglandin F1 alpha and tumor necrosis factor-alpha and prevented LPS-induced changes in cardiac output, arterial PO2, phagocyte activation, and peripheral leukocyte count. Changes in circulating concentrations of thromboxane B-2, mean pulmonary artery pressure, and dynamic pulmonary compliance were attenuated in the LPS//CAP18 group. Conclusions. Treatment with CAP18(106-137) neutralizes many of the deleterious effects of LPS in pigs.