Cardiotrophin-1 Attenuates Endotoxin-Induced Acute Lung Injury

• Published in: The Journal of surgical research 1999-06, Vol.84 (2), p.240-246
• Main Authors: Pulido, Edward J., Shames, Brian D., Pennica, Diane, O'Leary, Rhona M., Bensard, Denis D., Cain, Brian S., McIntyre, Robert C.
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Biological and medical sciences; Cyclic GMP - physiology; cytokine; Cytokines - pharmacology; Edema - chemically induced; Edema - prevention & control; Endotoxemia - pathology; Endotoxins; gp130; Injuries of the thorax. Foreign bodies. Diseases due to physical agents; lipopolysaccharide; Lung - pathology; Lung Diseases - chemically induced; Lung Diseases - pathology; Lung Diseases - physiopathology; Lung Diseases - prevention & control; Male; Medical sciences; Neutrophils - pathology; Pulmonary Circulation - drug effects; Pulmonary Circulation - physiology; rat; Rats; Rats, Sprague-Dawley; Traumas. Diseases due to physical agents; Vasodilation - drug effects; Vasodilation - physiology
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1999.5655

Cardiotrophin-1 (CT-1) is a recently discovered member of the gp130 cytokine family, which includes IL-6, IL-11, leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. Recent evidence suggests that, like other members of this family, CT-1 may possess anti-inflammatory properties. We hypothesized that in vivo CT-1 administration would attenuate endotoxin (ETX)-induced acute lung injury. We studied the effects of CT-1 (100 μg/kg ip, 10 min prior to ETX) in a rat model of ETX-induced acute lung injury (Salmonella typhimurium lipopolysaccharide, 20 mg/kg ip). Six hours after ETX, lungs were harvested for determination of neutrophil accumulation (myeloperoxidase, MPO, assay) and lung edema (wet-to-dry weight ratio). Mechanisms of pulmonary vasorelaxation were examined in isolated pulmonary artery rings at 6 h by interrogating endothelium-dependent (response to acetylcholine) and endothelium-independent (response to sodium nitroprusside) relaxation following α-adrenergic (phenylephrine)-stimulated preconstriction. CT-1 abrogated the endotoxin-induced lung neutrophil accumulation: 2.3 ± 0.2 units MPO/g wet lung (gwl) vs 6.3 ± 0.3 units MPO/gwl in the ETX group (P < 0.05 vs ETX, P > 0.05 vs control). Similarly, CT-1 prevented ETX-induced lung edema: wet-to-dry-weight ratio, 4.473 ± 0.039 vs 4.747 ± 0.039 in the ETX group (P < 0.05 vs ETX, P > 0.05 vs control). Endotoxin caused significant impairment of both endothelium-dependent and -independent pulmonary vasorelaxation, and CT-1 attenuated this injury. Thus, cardiotrophin-1 possesses significant anti-inflammatory properties in a model of endotoxin-induced acute lung injury.