Recombinant human interleukin-11 (rhlL-11) was evaluated in a New Zealand White rabbit model of endotoxemia. Animals received Escherichia coli LPS (150 μg/kg i.v.) via a femoral venous catheter. 30 min later, animals were treated with rhlL-11 (100 μg/kg i.v., n = 7), or rhlL-11 formulation buffer (n = 6). Arterial pressures were monitored for 6 h following rhlL-11. Approximately 5 h after LPS treatment, mean arterial pressure in vehicle-treated control animals was 46.7 mmHg, or 55% of group mean baseline, while that of rhlL-11-treated animals was 74.8 mmHg, or 94% of group mean baseline (P < 0.0005). Histologic evaluation of ileum, cecum and colon from rhlL-11-treated rabbits showed decreased hemorrhage, edema, and mucosal damage (P < 0.02), compared to the vehicle-treated controls. Intravenous LPS evokes hypotension mediated by the induction of inducible nitric oxide synthase (iNOS) and subsequent production of NO. Maintenance of blood pressure by rhIL-11 in LPS-treated rabbits in addition to the concurrent significant decrease in NO levels compared to vehicle-treated animals (P < 0.04) suggests that rhlL-11 interferes with the production of NO by iNOS and or the physiologic effects of NO on vascular smooth muscle.
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