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.(Arch Surg. 1995;130:1199-1208)