Antigen-induced bronchial hyperreactivity and bronchopulmonary inflammation in rats: effect of TNF receptor binding protein.
The effect of a receptor binding protein for tumor necrosis factor (TNFrbp) on cell infiltration, bronchial hyperreactivity, and release of inflammatory mediators were studied following antigen challenge in sensitized rats. A 3-fold increase in total cell number, mainly neutrophils and eosinophils, was noted in bronchoalveolar lavage (BAL) fluid 8 hours after antigen challenge. Antigen challenge also induced a significant hyperreactivity of the lower bronchus to carbachol and serotonin, but did not affect the reactivity of the trachea and upper bronchus. This increased responsiveness of the lower bronchus was transient, being detected 8 hours but not 24 hours after antigen challenge. Thromboxane B2 (TxB2), prostaglandin E2 (PGF2), and nitric oxide (NO) levels increased in the BAL fluid of sensitized rats 8 hours after antigen challenge by 197%, 172%, and 173%, respectively. TNFrbp treatment reduced by 83% the antigen-induced cell infiltration, with neutrophils being the cells most affected. The bronchial hyperreactivity induced by antigen challenge was also significantly inhibited by TNFrbp, whereas TxB2, PGE2, and NO levels in the BAL fluid were not affected. In our animal model, the cell infiltration and bronchial hyperreactivity appear to be mediated to some extent by TNF, but not by prostanoids nor NO.
Carvalho
C R
CR
Department of Pharmacology, Medical School, University of Sherbrooke, Quebec, Canada.
Jancar
S
S
Conroy
D
D
Sirois
P
P
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D001996:Bronchopneumonia / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D002217:Carbachol / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D015232:Dinoprostone / Q000032:analysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects; D009569:Nitric Oxide / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D012701:Serotonin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000032:analysis; D053319:Tumor Necrosis Factor Decoy Receptors
D002352:Carrier Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; C069521:recombinant human tumor necrosis factor-binding protein-1; D009569:Nitric Oxide; D012701:Serotonin; D013929:Thromboxane B2; D002217:Carbachol; D015232:Dinoprostone