Effect of interleukin-1 receptor antagonist on antigen-induced pulmonary responses in guinea pigs.
The ability of the human interleukin-1 receptor antagonist, IL-1ra, to inhibit aerosolized antigen-induced airway hyperreactivity to i.v. substance P and bronchoalveolar lavage inflammatory cell accumulation, under in vivo conditions, was assessed in guinea pigs. Pretreatment with IL-1ra (30 mg/kg i.p., administered 30 min prior to antigen challenge) inhibited increases in bronchoalveolar lavage fluid neutrophil accumulation at 1 h following aerosolized antigen (0.1% ovalbumin for 30 min) exposure. IL-1ra (30 mg/kg i.p., administered 30 min pre-antigen and 3 h post-antigen) also significantly attenuated antigen-induced increases in bronchoalveolar lavage fluid leukocytes at 6 h following antigen. However, IL-1ra (30 mg/kg i.p., administered 30 min pre-antigen as well as 6 and 12 h post-antigen) did not affect antigen-induced bronchoalveolar lavage fluid leukocyte accumulation at 24 h following antigen. A limited, but significant (P less than 0.05), reduction in antigen-induced airway hyperreactivity to 10 micrograms/kg, but not lower doses, of i.v. substance P (measured as peak increases in lung resistance in cm H2O/ml per s) at 6 h following antigen was noted in the presence of IL-1ra (30 mg/kg i.p.). In conclusion, IL-1ra inhibited antigen-induced airway hyperreactivity to i.v. substance P and bronchoalveolar lavage fluid inflammatory leukocyte influx in the guinea pig, in a time-dependent manner, suggesting that cytokines, such as IL-1, may contribute to the pathophysiology surrounding this pulmonary anaphylaxis model.
Selig
W
W
Department of Pharmacology, Hoffmann-La Roche, Nutley, NJ 07110.
Tocker
J
J
D000336:Aerosols; D000707:Anaphylaxis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology; D006168:Guinea Pigs; D006801:Humans; D007958:Leukocyte Count; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D011014:Pneumonia / Q000473:pathology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D017472:Receptors, Interleukin-1; D012680:Sensitivity and Specificity; D013373:Substance P / Q000037:antagonists & inhibitors; D013997:Time Factors
D000336:Aerosols; D000941:Antigens; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D013373:Substance P