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 antibody to E- and L-selectin, EL-246, in a postonset model of sepsis. DESIGN: Nonrandomized controlled study. STUDY SUBJECTS: Young Yorkshire swine. INTERVENTIONS: Three groups were studied. Controls (n = 8) received 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 pulmonary hemodynamics, arterial blood gas determination, bronchoalveolar lavage protein and neutrophil content, neutrophil integrin and selectin expression, neutrophil oxidant burst, and organ myeloperoxidase content. RESULTS: Treatment with EL-246 significantly reduced lung injury, as indicated by improved bronchoalveolar lavage protein and neutrophil content, resulting in a significant improvement in arterial oxygenation. This reduction in lung injury was produced by a reduction in lung myeloperoxidase content. Treatment with EL-246 failed to prevent the development of pulmonary hypertension and systemic hypotension. Neutrophils from animals with sepsis exhibited significant activation and upregulation of CD18, shedding of L-selectin, and production of increased levels of oxidants compared with controls. CONCLUSION: Treatment of animals with EL-246 soon the onset of sepsis produced significant protection against acute lung injury but failed to attenuate hemodynamic derangements associated with sepsis.