title: Corticosteroids suppress in vitro tonsillar proliferation in children with obstructive sleep apnoea.
abstract: 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.
authors.affiliation: Department of Pediatrics, Division of Sleep Medicine, Kosair Children's Hospital Research Institute, University of Louisville, Louisville, KY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kheirandish-Gozal
authors.forename: L D
authors.initials: LD
authors.lastname: Serpero
authors.forename: E
authors.initials: E
authors.lastname: Dayyat
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: J L
authors.initials: JL
authors.lastname: Goldman
authors.forename: A
authors.initials: A
authors.lastname: Snow
authors.forename: R
authors.initials: R
authors.lastname: Bhattacharjee
authors.forename: D
authors.initials: D
authors.lastname: Gozal
mesh_terms: D000233:Adenoidectomy; D000234:Adenoids / Q000187:drug effects* / Q000473:pathology; D000704:Analysis of Variance; D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002648:Child; D016207:Cytokines / Q000032:analysis; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006984:Hypertrophy; D008297:Male; D014066:Palatine Tonsil / Q000187:drug effects* / Q000473:pathology; D017286:Polysomnography; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D018709:Statistics, Nonparametric; D014068:Tonsillectomy
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D003907:Dexamethasone; D000068298:Fluticasone