Effect of interleukin 13 on bronchial hyperresponsiveness and the bronchoprotective effect of beta-adrenergic bronchodilators and corticosteroids.
BACKGROUND
Fluticasone affects airway bronchial hyperresponsiveness (BHR) and enhances bronchodilation and bronchoprotection induced by beta-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 beta-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% (PC200) was calculated. We compared this response to methacholine in control mice with the response after treatment with IL-13 receptor alpha 2-IgGFc fusion protein (IL-13R alpha 2) (an IL-13 blocker), fluticasone, albuterol, salmeterol, fluticasone-albuterol, and fluticasone-salmeterol.


RESULTS
IL-13R alpha 2 (PC200, 17.59) completely blocks the BHR-induced effects of IL-13 (PC200, 7.28; P < .005). After IL-13 therapy (PC200, 5.90; P < .005), 1 mg/mL of albuterol (PC200, 3.38; P = .33), fluticasone (PC200, 4.59; P = .40), or fluticasone plus 50 microg/mL of salmeterol (PC200, 5.59; P = .11) showed no significant bronchoprotection. In nonsensitized mice, fluticasone plus 0.25 microg/mL of salmeterol (PC200, 25.90; P < .005) showed significantly greater bronchoprotection than did salmeterol alone (PC200, 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, beta-agonists, and fluticasone plus beta-agonists are significantly less in IL-13-treated mice than in nonsensitized or ovalbumin-sensitized mice.
Division of Allergy/Immunology, Creighton University, Omaha, Nebraska 68131, USA. rtownley@creighton.edu
Robert G
RG
Townley
Pradeep R
PR
Gendapodi
Nidal
N
Qutna
Joseph
J
Evans
Francisco A
FA
Romero
Peter
P
Abel
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D000068298:Fluticasone; D000068297:Fluticasone-Salmeterol Drug Combination; D018793:Interleukin-13 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000008:administration & dosage; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D000068299:Salmeterol Xinafoate
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D016210:Methacholine Chloride; D000068299:Salmeterol Xinafoate; D010047:Ovalbumin; D000068298:Fluticasone; D000420:Albuterol