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Cardiotrophin-1 attenuates endotoxin-induced acute lung injury
E J Pulido1, B D Shames, D Pennica
1Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado, 80262, USA.
Insights
Cardiotrophin-1 (CT-1) administration reduced inflammation and lung injury caused by endotoxin (ETX) in rats. This cytokine shows promise as an anti-inflammatory therapy for acute lung injury.
Area of Science:
- Biochemistry
- Immunology
- Pulmonary Medicine
Background:
- Cardiotrophin-1 (CT-1) is a cytokine in the gp130 family with potential anti-inflammatory effects.
- Acute lung injury (ALI) can be induced by endotoxin (ETX), leading to significant inflammation and edema.
Purpose of the Study:
- To investigate the in vivo anti-inflammatory effects of CT-1 in a rat model of ETX-induced ALI.
- To determine if CT-1 administration can attenuate lung neutrophil accumulation and edema.
Main Methods:
- Rats were treated with CT-1 prior to ETX injection.
- Lung neutrophil infiltration was measured using myeloperoxidase (MPO) assay.
- Lung edema was assessed by wet-to-dry weight ratio.
- Pulmonary vasorelaxation was evaluated in isolated pulmonary artery rings.
Main Results:
- CT-1 significantly reduced ETX-induced neutrophil accumulation in the lungs (P < 0.05).
- CT-1 administration prevented ETX-induced lung edema (P < 0.05).
- CT-1 attenuated the impairment of endothelium-dependent and -independent pulmonary vasorelaxation caused by ETX.
Conclusions:
- CT-1 exhibits significant anti-inflammatory properties in a model of ETX-induced ALI.
- CT-1 may be a potential therapeutic agent for ALI and related inflammatory conditions.
Abstract:
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 microgram/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 alpha-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.