BODY TO E-SELECTIN AND L-SELECTIN DOES NOT PREVENT LUNG INJURY OR MORTALITY IN SEPTIC BABOONS

Recruitment of polymorphonuclear leukocytes (PMN) through upregulation of cellular adhesion molecules is a proposed mechanism of injury in s epsis and acute respiratory distress syndrome (ARDS). We hypothesized that pretreatment of baboons with a monoclonal antibody to human E-and L-selectin (EL-246) during sepsis would decrease PMN influx into tiss ues and result in less organ injury during gram-negative sepsis. We st udied 14 anesthetized, ventilated adult baboons; six animals received 1 mg/kg of EL-246 before infusion of an LD100 of live Escherichia coli and six received the E. coli infusion without antibody therapy. Two o ther animals received 1 mg/kg of EL-246 intravenously without an infus ion of bacteria. Intermittent measurements were made of circulatory pr essures, cardiac output, urine output, arterial blood gases, ventilati on:perfusion ratio ((V) over dot A/(Q) over dot ), and hematologic sta tus. The experiments were ended at 48 h or at the time of death. Tissu es were harvested for pathology and biochemical measurements. The E. c oli infusions were associated with a hyperdynamic state, pulmonary hyp ertension, systemic hypotension, decreased urine output (UOP), and met abolic acidosis. The antibody partly blocked PMN migration, but there were few significant physiologic or biochemical differences between th e EL-246-treated and untreated animals. In the antibody-treated animal s, UOP was decreased, metabolic acidosis was worsened, and median surv ival time was decreased significantly. We conclude that treatment with an antibody to E-and L-selectin in gram-negative sepsis does not impr ove gas exchange or protect against lung injury, and is associated wit h decreased survival time in primates.