Eur Respir J 2008, doi:10.1183/09031936.00130608
Corticosteroids Suppress In vitro Tonsillar Proliferation in Children with Obstructive Sleep apnoea
1 Division of Sleep Medicine and Kosair Children's Hospital Research Institute
* To whom correspondence should be addressed. E-mail: david.gozal{at}louisville.edu.
Intranasal corticosteroids (CS) are potentially useful interventions for children with OSA, and may reduce lymphadenoid tissue size in the upper airway. We hypothesized that CS would reduce cellular proliferation and production of pro-inflammatory cytokines in a tonsil/adenoid mixed-cell culture system. Dissociated tonsils or adenoids harvested intra-operatively from children with polysomnographically-diagnosed OSA were cultured in control medium (CO) or after stimulation with LPS and concanavalin A (STIM), and incubated with dexamethasone (DEXA; 10-5-–10-7M), fluticasone (FLU; 10-5–10-14M), and budesonide (BUD; 10-4–10-14 M). Proliferation and apoptosis were assessed, and supernatants were assayed for cytokines TNF- STIM increased tonsillar and adenoidal proliferation compared to CO (1976±133 cpm vs. 404±69 cpm; p<0.00001; n=54). DEX, FLU, and BUD reduced cellular proliferation rates, and exhibited dose-dependent effects, with the potency being FLU>BUD>DEX (p<0.0001; n=25/group). Conversely, CS increased cellular apoptosis (n=20/group; p<0.0001). Furthermore, TNF- Whole tissue cell cultures of adenoids and tonsils provide a useful approach for in vitro assessment of therapeutic efficacy of CS in the management of the lymphadenoid hypertrophy that underlies OSA in children. Keywords: Children, corticosteroids, cytokines, inflammation, obstructive sleep apnoea, proliferation, T lymphocytes, tonsillar hypertrophy
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