Effects of IL-13 on airway responses in the guinea pig.
Levels of interleukin (IL)-13 are increased in asthmatic airways. IL-13 has been shown to be necessary and sufficient for allergen-induced airway hyperresponsiveness and increased inflammatory cell counts in bronchoalveolar lavage (BAL) fluid in a murine model of asthma but is thought to protect against airway inflammation when low doses are provided to the guinea pig lung. To determine the role of IL-13 in the guinea pig, we studied the effects of a 360-microg/kg dose of nebulized IL-13 in naive animals and of IL-13 abrogation after airway challenge of sensitized animals. Nebulized IL-13 significantly decreased the dose of histamine required to double baseline respiratory system resistance (ED(100), 22 +/- 3 vs. 13 +/- 2 nmol/kg; P < 0.05) and was associated with recovery of significantly greater numbers of macrophages, lymphocytes, eosinophils, and neutrophils in BAL fluid. Guinea pigs pretreated with a fusion protein that binds IL-13 [soluble IL-13 receptor alpha2 (sIL-13Ralpha2)] were protected from developing antigen-induced airway hyperresponsiveness (ED(100), 210 +/- 50 vs. 20 +/- 10 nmol/kg; P <0.01). sIL-13Ralpha2 (2 doses of 20 mg/kg) significantly reduced the histological grade of allergen-induced lung eosinophil accumulation, whereas the effects of two doses of 10 mg/kg were not significant. These findings demonstrate that the tissue levels of IL-13 induced by allergen challenge of sensitized animals induce airway hyperresponsiveness and inflammation and that IL-13 is required for the expression of allergen-induced airway hyperresponsiveness in the guinea pig ovalbumin model.
Morse
Brian
B
Combined Program in Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Sypek
Joseph P
JP
Donaldson
Debra D
DD
Haley
Kathleen J
KJ
Lilly
Craig M
CM
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology*; D004804:Eosinophils / Q000473:pathology; D006168:Guinea Pigs; D018793:Interleukin-13 / Q000494:pharmacology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D020033:Protein Isoforms / Q000502:physiology; D018123:Receptors, Interleukin / Q000502:physiology; D053660:Receptors, Interleukin-13
D000941:Antigens; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D020033:Protein Isoforms; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13