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Recombinant human interleukin-11 prevents hypotension in LPS-treated anesthetized rabbits

Preclinical R & D, Genetics Institute, Inc., Cambridge, Massachusetts, USA, Tmisra{at}genetics.com

T.J. Ferranti

Preclinical R & D, Genetics Institute, Inc., Cambridge, Massachusetts, USA

L.H. Donnelly

Preclinical R & D, Genetics Institute, Inc., Cambridge, Massachusetts, USA

J.E. Erickson

Preclinical R & D, Genetics Institute, Inc., Cambridge, Massachusetts, USA

R.G. Schaub

Preclinical R & D, Genetics Institute, Inc., Cambridge, Massachusetts, USA

J.C. Keith

Preclinical R & D, Genetics Institute, Inc., Cambridge, Massachusetts, USA

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.

Innate Immunity, Vol. 3, No. 4, 297-305 (1996)
DOI: 10.1177/096805199600300403


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