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Published on: April 14, 2010
The IL-5 receptor on human bronchus selectively primes for hyperresponsiveness
Charles A Rizzo1, Richard Yang, Scott Greenfeder
1Allergy, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Interleukin-5 (IL-5) directly increases human bronchial hyperresponsiveness, independent of eosinophils. This suggests IL-5 may directly contribute to asthma symptoms by affecting airway tissue.
Area of Science:
- Immunology
- Respiratory Medicine
- Pharmacology
Background:
- The role of IL-5-induced eosinophilia in airway hyperresponsiveness is debated.
- Eosinophil-independent IL-5 effects on airway hyperresponsiveness have been observed in animal models.
Purpose of the Study:
- To investigate the direct effects of IL-5 on human bronchial responsiveness.
- To determine if IL-5 influences airway contractility independent of eosinophils.
Main Methods:
- Human bronchus, jejunum, and saphenous vein tissues were incubated with recombinant human IL-5 (rhIL-5).
- Contractility to acetylcholine and phenylephrine was measured.
- RT-PCR assessed IL-5 receptor alpha (IL-5Rα) and CCR3 expression in various tissues.
Main Results:
- rhIL-5 significantly enhanced bronchial contractility to acetylcholine in a dose-dependent manner.
- This effect was blocked by antibodies against IL-5 and IL-5Rα.
- rhIL-5 did not affect contractility in saphenous vein or jejunum.
- IL-5Rα expression was highest in bronchial muscle, with lower expression in other tissues.
Conclusions:
- IL-5 receptor expression is tissue-selective in airways.
- IL-5 can directly induce bronchial hyperresponsiveness, independent of eosinophils.
- Elevated IL-5 in asthma may directly contribute to bronchial hyperresponsiveness.
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