Asthma and lower airway diseaseEnhanced production of IL-17A in patients with severe asthma is inhibited by 1α,25-dihydroxyvitamin D3 in a glucocorticoid-independent fashion
Section snippets
Subjects
Healthy adults (study approved by the local research ethics committee, 09/H0804/77) and asthmatic patients (08/H0804/84) were recruited. All healthy control subjects and patients provided written informed consent. Asthmatic patients had moderate-to-severe asthma for at least 6 months on therapy step 3 or 4 of the British Thoracic Society guidelines on the management of asthma diagnosed by a specialist physician. The average inhaled corticosteroid dose in beclomethasone diproprionate equivalents
Comparison of IL-17A and IL-22 production by PBMCs in culture from patients with SS and patients with SR asthma
Details of the 2 cohorts of patients with moderate-to-severe asthma, defined as SS or SR asthma on the basis of changes in lung function after a 2-week course of oral prednisolone, and of healthy nonasthmatic control subjects are provided in the Methods section. Notably, these 2 patient groups exhibited comparable disease severity based on impairment of lung function and were taking comparable doses of inhaled corticosteroids (total dosages based on beclomethasone dipropionate equivalence).
Discussion
Our data demonstrate that the production of IL-17A and IL-22 by human peripheral blood CD4+ T cells is increased in patients with severe asthma. Notably, IL-17A levels, but not IL-22 levels, were approximately 5-fold greater in patients with SR asthma compared with those seen in patients with SS asthma. Strikingly, the glucocorticoid dexamethasone significantly enhanced the frequency of IL-17A+ cells in culture in both nonasthmatic control subjects and asthmatic patients, although IL-17A
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Supported by Asthma UK through project grants 08/040 and 11/040. A.M.N. is funded by Asthma UK. E.S.C. is funded by an MRC British Thoracic Society/Morriston Davies Trust Capacity Building PhD Studentship. K.R. was in receipt of an MRC Clinical Training Research Fellowship. The research was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.
Disclosure of potential conflict of interest: E. S. Chambers has received an MRC Centenary Award and has received a BSI International Travel Grant. K. Ryanna has received an MRC Clinical Research Training Fellowship. C. J. Corrigan has received honoraria for consultancy from Meda and from Chiesi, has received one or more grants from or has one or more grants pending with and has received one or more payments for travel/accommodations/meeting expenses from Novartis, and has received honoraria for lectures from Allergy Therapeutics. C. M. Hawrylowicz has been supported by one or more grants from Asthma UK and has received an Ancillary grant from the National Institutes of Health, a Wellcome Trust Clinical Research Training Fellowship, and MRC PhD studentships. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.