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.