Effect of interleukin 13 on bronchial hyperresponsiveness and the bronchoprotective effect of β-adrenergic bronchodilators and corticosteroids

Robert G. Townley, Pradeep R. Gendapodi, Nidal Qutna, Joseph Evans, Francisco A. Romero, Peter W. Abel

Research output: Contribution to journalArticle

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Abstract

Background: Fluticasone affects airway bronchial hyperresponsiveness (BHR) and enhances bronchodilation and broncho-protection induced by β-adrenergic agonists. Interleukin 13 (IL-13), however, induces BHR. Objective: To test the hypotheses that fluticasone inhibits BHR after either allergen sensitization or IL-13 administration and that fluticasone restores the bronchodilation and bronchoprotective effects of β-agonists. Methods: The BHR to methacholine induced by IL-13 or ovalbumin was determined in BALB/c mice, and the provocation concentration of methacholine that caused an increase in enhanced pause in expiration of 200% (PC 200) was calculated. We compared this response to methacholine in control mice with the response after treatment with IL-13 receptor α 2-IgGFc fusion protein (IL-13Rα2) (an IL-13 blocker), fluticasone, albuterol, salmeterol, fluticasone-albuterol, and fluticasone-salmeterol. Results: IL-13Rα2 (PC 200, 17.59) completely blocks the BHR-induced effects of IL-13 (PC 200, 7.28; P ≤.005). After IL-13 therapy (PC 200, 5.90; P ≤.005), 1 mg/mL of albuterol (PC 200, 3.38; P =.33), fluticasone (PC 200, 4.59; P =.40), or fluticasone plus 50 μg/mL of salmeterol (PC 200, 5.59; P =.11) showed no significant bronchoprotection. In nonsensitized mice, fluticasone plus 0.25 μg/mL of salmeterol (PC 200, 25.90; P ≤.005) showed significantly greater bronchoprotection than did salmeterol alone (PC 200, 11.08; P =.26). Fluticasone plus 0.3 mg/mL of albuterol and fluticasone plus 1 mg/mL of albuterol were significantly more protective than was fluticasone or albuterol alone in ovalbumin-sensitized mice. Conclusions: The protective effects of fluticasone, βagonists, and fluticasone plus β-agonists are significantly less in IL-13-treated mice than in nonsensitized or ovalbumin-sensitized mice.

Original languageEnglish
Pages (from-to)190-197
Number of pages8
JournalAnnals of Allergy, Asthma and Immunology
Volume102
Issue number3
Publication statusPublished - Mar 2009

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Pulmonary and Respiratory Medicine

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