Induction of leucocyte recruitment and bronchial hyperresponsiveness in the guinea pig by aerosol administration of interleukin-2.
Exposure of guinea pigs to an aerosol of human recombinant interleukin-2 (IL-2; 30 micrograms) resulted in an increase in the numbers of eosinophils and macrophages recovered from bronchoalveolar lavage fluid (BALF) 24 h later. This was accompanied by a bronchial hyperresponsiveness to intravenous acetylcholine. In guinea pigs sensitized to ovalbumin, exposure to IL-2 caused an increase in the number of macrophages, but not eosinophils in BALF and bronchial hyperresponsiveness to acetylcholine did not develop. In guinea pig skin, intradermal injection of IL-2 (10(-14) to 10(-9) mol/site) had no effect on 111In-eosinophil accumulation, measured over 3 h, suggesting that IL-2 does not act directly to recruit eosinophils. The hypothesis that IL-2 may be acting via release of interleukin-5 (IL-5) was tested using an antibody to IL-5 (TRFK-5; 1 mg/kg). Treatment with TRFK-5 1 h before exposure to IL-2 aerosol had no effect on the numbers of macrophages or eosinophils recovered from BALF 24 h later, although there was a tendency for reduced bronchial hyperresponsiveness to acetylcholine. These results suggest that (1) IL-2 is not a directly acting chemoattractant for eosinophils in the guinea pig, (2) the action of IL-2 to increase bronchial hyperresponsiveness is also indirect, partly via generation of IL-5, and (3) immunological sensitization alters the response of both eosinophils and bronchial smooth muscle to IL-2.
Milne
A A
AA
Department of Pharmacology, Royal College of Surgeons, UK.
Teixeira
M M
MM
Hellewell
P G
PG
Piper
P J
PJ
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000473:pathology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006168:Guinea Pigs; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D015848:Interleukin-5 / Q000276:immunology; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D000336:Aerosols; D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015848:Interleukin-5; D011994:Recombinant Proteins; D010047:Ovalbumin