RECOMBINANT HUMAN INTERLEUKIN-11 PREVENTS HYPOTENSION IN LPS-TREATED ANESTHETIZED RABBITS

Recombinant human interleukin-11 (rhIL-11) was evaluated in a New Zeal and White rabbit model of endotoxemia. Animals received Escherichia co li LPS (150 mu g/kg i.v.) via a femoral venous catheter. 30 min later, animals were treated with rhIL-11 (100 mu g/kg i.v., n = 7), or rhIL- 11 formulation buffer (n = 6). Arterial pressures were monitored for 6 h following rhIL-11. Approximately 5 h after LPS treatment, mean arte rial pressure in vehicle-treated control animals was 46.7 mmHg, or 55% of group mean baseline, while that of rhIL-11-treated animals was 74. 8 mmHg, or 94% of group mean baseline (P < 0.0005). Histologic evaluat ion of ileum, cecum and colon from rhIL-11-treated rabbits showed decr eased hemorrhage, edema, and mucosal damage (P < 0.02), compared to th e vehicle-treated controls. Intravenous LPS evokes hypotension mediate d by the induction of inducible nitric oxide synthase (iNOS) and subse quent production of NO. Maintenance of blood pressure by rhIL-11 in LP S-treated rabbits in addition to the concurrent significant decrease i n NO levels compared to vehicle-treated animals (P < 0.04) suggests th at rhIL-11 interferes with the production of NO by iNOS and or the phy siologic effects of NO on vascular smooth muscle.