SEPSIS-INDUCED ACUTE LUNG INJURY IS ATTENUATED BY SELECTIN BLOCKADE FOLLOWING THE ONSET OF SEPSIS

Objective: To determine the effect of infusion with a dual-binding ant ibody to E- and L-selectin, EL-246, in a postonset model of sepsis. De sign: Nonrandomized controlled study. Study Subjects: Young Yorkshire swine. Interventions: Three groups were studied. Controls (n=8) receiv ed saline solution only. Untreated animals with sepsis (n=8) received a 1-hour intravenous infusion of live Pseudomonas aeruginosa. Animals treated with EL-246 (n=6) received the same bacterial infusion and a 2 -mg/kg bolus of EL-246 at 30 minutes. Outcome Measures: Systemic and p ulmonary hemodynamics, arterial blood gas determination, bronchoalveol ar lavage protein and neutrophil content, neutrophil integrin and sele ctin expression, neutrophil oxidant burst, and organ myeloperoxidase c ontent. Results: Treatment with EL-246 significantly reduced lung inju ry, as indicated by improved bronchoalveolar lavage protein and neutro phil content, resulting in a significant improvement in arterial oxyge nation. This reduction in lung injury was produced by a reduction in l ung myeloperoxidase content. Treatment with EL-246 failed to prevent t he development of pulmonary hypertension and systemic hypotension. Neu trophils from animals with sepsis exhibited significant activation and upregulation of CD18, shedding of L-selectin, and production of incre ased levels of oxidants compared with controls. Conclusion: Treatment of animals with EL-246 soon the onset of sepsis produced significant p rotection against acute lung injury but failed to attenuate hemodynami c derangements associated with sepsis.