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Published online before print December 1, 2008, 10.1183/09031936.00130608
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Eur Respir J 2009; 33:1077-1084
Copyright ©ERS Journals Ltd 2009

Corticosteroids suppress in vitro tonsillar proliferation in children with obstructive sleep apnoea

L. Kheirandish-Gozal1, L. D. Serpero1, E. Dayyat1, J. Kim1, J. L. Goldman2, A. Snow1, R. Bhattacharjee1 and D. Gozal1

1 Division of Sleep Medicine and Kosair Children's Hospital Research Institute, Dept of Pediatrics, 2 Dept of Surgery, University of Louisville, Louisville, KY, USA.

CORRESPONDENCE: D. Gozal, Dept of Pediatrics,, Comer Children's Hospital, The University of Chicago, 5721 S. Maryland Avenue, MC 8000, Suite K-160, Chicago, IL 60637, USA. Fax: 1 7737024523. E-mail: dgozal{at}peds.bsd.uchicago.edu

Keywords: Corticosteroids, cytokines, inflammation, obstructive sleep apnoea, T-lymphocytes, tonsillar hypertrophy

Received: August 24, 2008
Accepted November 8, 2008

Intranasal corticosteroids (CS) are potentially useful interventions for children with obstructive sleep apnoea (OSA), and may reduce lymphadenoid tissue size in the upper airway. The present authors hypothesised that CS would reduce cellular proliferation and the 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 lipopolysaccharide and concanavalin A (STIM), and incubated with dexamethasone (DEX; 10–5–10–7 M), fluticasone (FLU; 10–5–10–14 M) and budesonide (BUD; 10–4–10–14 M). Proliferation and apoptosis were assessed, and supernatants were assayed for the cytokines tumour necrosis factor (TNF)-{alpha}, interleukin (IL)-6 and IL-8.

STIM increased tonsillar and adenoidal proliferation compared with CO (1,976±133 versus 404±69 counts·min–1; n = 54). DEX, FLU and BUD reduced cellular proliferation rates, and exhibited dose-dependent effects, with the potency being FLU>BUD>DEX (n = 25 per group). Conversely, CS increased cellular apoptosis (n = 20 per group). Furthermore, TNF-{alpha}, IL-8 and IL-6 concentrations in the supernatant were increased by STIM, and markedly reduced by all CS (n = 48 per group).

Whole tissue cell cultures of adenoids and tonsils provide a useful approach for in vitro assessment of therapeutic efficacy of corticosteroids in the management of lymphadenoid hypertrophy that underlies obstructive sleep apnoea in children.







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