Effects of interleukin-10 and modulators of cyclic AMP formation on endotoxin-induced inflammation in rat lung.

Abstract

The aim of this study was to investigate the effects of IL-10, a cell permeable analogue of cyclic AMP, dibutyryl-cAMP (db-cAMP), modulators of intracellular cyclic AMP such as phosphodiesterase (PDE) inhibitors and a beta 2-adrenoceptor agonist, salmeterol, on pulmonary inflammation following acute lung injury induced by endotoxin exposure in rats. Pulmonary inflammation was induced in adult Wistar rats by a 60-min exposure to endotoxin (lipopolysaccharide, LPS, 100 micrograms/mL). 4 h later bronchoalveolar lavage (BAL) was performed. The PDE inhibitors, rolipram (3 and 5 mg/kg) and theophylline (30 and 100 mg/kg) inhibited neutrophil recruitment, TNF-alpha release and cellular activation in BAL. Salmeterol (0.5 mg/mL) and IL-10 (0.1 microgram) only inhibit TNF-alpha increase in the BAL fluid and db-AMPc (2.5 micrograms/rat) was ineffective. The present data show that the selective PDE4 inhibitor, rolipram, and the non-selective PDE inhibitor, theophylline, markedly reduced the pulmonary inflammation associated with acute lung injury in the rat. These effects may be mediated in part by IL-10 rather than by cyclic AMP, as demonstrated by the potent inhibitory activity of exogenous IL-10 on the increase in TNF-alpha release in BAL fluid of rats exposed to LPS.

• Authors: N Escofier, E Boichot, N Germain, P M Silva, M A Martins, V Lagente
• Journal: Fundamental & clinical pharmacology (Fundam Clin Pharmacol) Vol. 13 Issue 1 Pg. 96-101 ( 1999) ISSN: 0767-3981 [Print] England
• PMID: 10027094 (Publication Type: Journal Article)

Chemical References

• Adrenergic beta-Agonists
• Endotoxins
• Free Radical Scavengers
• Lipopolysaccharides
• Phosphodiesterase Inhibitors
• Pyrrolidinones
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Luminol
• Bucladesine
• Salmeterol Xinafoate
• Zymosan
• Theophylline
• Cyclic AMP
• Superoxide Dismutase
• Rolipram
• Albuterol

Topics

• Administration, Inhalation
• Adrenergic beta-Agonists (pharmacology)
• Albuterol (analogs & derivatives, pharmacology)
• Animals
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Bucladesine (pharmacology)
• Cell Count (drug effects)
• Cyclic AMP (metabolism)
• Dose-Response Relationship, Drug
• Endotoxins (pharmacology)
• Free Radical Scavengers (pharmacology)
• Inflammation (chemically induced, prevention & control)
• Interleukin-10 (pharmacology)
• Lipopolysaccharides (pharmacology)
• Luminescent Measurements
• Luminol
• Lung (drug effects, pathology)
• Male
• Neutrophils (cytology, pathology)
• Phosphodiesterase Inhibitors (pharmacology)
• Pyrrolidinones (pharmacology)
• Rats
• Rats, Wistar
• Rolipram
• Salmeterol Xinafoate
• Superoxide Dismutase (pharmacology)
• Theophylline (pharmacology)
• Tumor Necrosis Factor-alpha (drug effects, metabolism)
• Zymosan (pharmacology)