Am. J. Respir. Crit. Care Med., Volume 163, Number 3, March 2001, 665-673

Antibody to Intercellular Adhesion Molecule 1 (CD54) Decreases Survival and Not Lung Injury in Baboons with Sepsis

KAREN E. WELTY-WOLF, MARTHA S. CARRAWAY, YU-CHIN T. HUANG, STEVEN G. SIMONSON, STEPHEN P. KANTROW, TAKASHI K. KISHIMOTO, and CLAUDE A. PIANTADOSI

Department of Medicine, Durham VA Medical Center and Duke University Medical Center, Durham, North Carolina; Astra-Zeneca, Wilmington, Delaware; Department of Medicine, Louisiana State University, New Orleans, Louisiana; and Boehringer-Ingelheim, Ridgefield, Connecticut

Neutrophil influx into the lung is an important event in the pathogenesis of acute lung injury in gram-negative sepsis. We hypothesized that administration of a monoclonal antibody to intercellular adhesion molecule 1 (ICAM-1, CD54), a molecule mediating neutrophil adhesion to endothelial cells, would decrease neutrophil sequestration and transmigration in the lung and attenuate lung injury in Escherichia coli sepsis. Sepsis was induced in 12 baboons primed with heat-killed E. coli (1 × 10⁹ CFU/kg) 12 h before infusion of live bacteria (1 × 10¹⁰ CFU/kg). Six animals received monoclonal antibody to CD54 (1 mg/kg) intravenously at the time of live E. coli infusion. After 48 h or when blood pressure could not be maintained, tissues were harvested and bronchoalveolar lavage (BAL) samples were obtained. Median survival time was decreased in anti-CD54-treated animals. This group also had decreased mean arterial pressure, increased metabolic acidosis, and decreased urine output. Measures of lung injury including gas exchange, lung lavage protein and lactate dehydrogenase (LDH), lung thiobarbituric acid-reactive species, and lung histology, including alveolar neutrophil volumes, were unaffected by treatment. The effect of anti-CD54 on neutrophil influx into tissues as measured by myeloperoxidase was organ specific. These data show that monoclonal antibody to CD54 does not ameliorate acute lung injury in E. coli sepsis, and septic primates given anti-CD54 have worsened metabolic parameters and decreased survival.

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