November 1995

Sepsis-Induced Acute Lung Injury Is Attenuated by Selectin Blockade Following the Onset of Sepsis

Author Affiliations

From the Departments of Surgery (Drs Ridings, Bloomfield, Windsor, and Sugerman), Pediatrics (Dr Holloway), and Medicine (Dr Fowler), Medical College of Virginia, Virginia Commonwealth University, Richmond, and the Department of Veterinary Molecular Biology, Montana State University, Bozeman (Dr Jutila).

Arch Surg. 1995;130(11):1199-1208. doi:10.1001/archsurg.1995.01430110057011

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)