Cytokines contribute to airway dysfunction in antigen-challenged guinea pigs: inhibition of airway hyperreactivity, pulmonary eosinophil accumulation, and tumor necrosis factor generation by pretreatment with an interleukin-1 receptor antagonist.
The role of pro-inflammatory cytokines in an animal model of allergic lung disease was examined by use of an interleukin-1 receptor antagonist (IL-1ra) and a specific bioassay for tumor necrosis factor (TNF). Ovalbumin-sensitized guinea pigs exhibit a marked bronchial hyperreactivity (assessed by airway responsiveness to intravenous histamine) and pulmonary eosinophil accumulation (assessed by bronchoalveolar lavage) 24 h after challenge with aerosolized antigen. Exposure of animals to an aerosol of IL-1ra (50 micrograms over 30 min) immediately before antigen challenge resulted in a marked protection against bronchial hyperreactivity and pulmonary eosinophil accumulation compared with IL-1ra vehicle-pretreated animals. Additionally, we report for the first time generation of TNF bioactivity in the bronchoalveolar lavage of antigen-challenged animals, which was significantly reduced in animals exposed to aerosolized IL-1ra before challenge. These studies point to a key role for the cytokines IL-1 and possibly TNF in the pulmonary changes observed during allergic airway disease.
Watson
M L
ML
Department of Pharmacology, University of Bath, United Kingdom.
Smith
D
D
Bourne
A D
AD
Thompson
R C
RC
Westwick
J
J
D000336:Aerosols; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D006168:Guinea Pigs; D007249:Inflammation; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000336:Aerosols; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha