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 ; n554). DEX, FLU and BUD reduced cellular proliferation rates, and exhibited dose-dependent effects, with the potency being FLU.BUD.DEX (n525 per group). Conversely, CS increased cellular apoptosis (n520 per group). Furthermore, TNF-a, IL-8 and IL-6 concentrations in the supernatant were increased by STIM, and markedly reduced by all CS (n548 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.

Transcriptomic Analysis Identifies Phosphatases as Novel Targets for Adenotonsillar Hypertrophy of Pediatric Obstructive Sleep Apnea

“…Furthermore, we recently used adenotonsillar cell culture assays to confirm that these pharmacologic interventions promote an antiproliferative phenotype (13,35). The current study provides a much broader framework for the selection of novel candidate pathways and critical mediators of adenotonsillar hypertrophy in children with OSA.…”

“…To detect global cell, T-cell, and B-cell specific proliferation, we used bromodeoxyuridine pulsed proliferation analysis using flow cytometry (13). A similar approach was undertaken using annexin V mouse antihuman antibodies to quantify global, T-cell, or B-cell specific apoptosis (13).…”

“…A similar approach was undertaken using annexin V mouse antihuman antibodies to quantify global, T-cell, or B-cell specific apoptosis (13). All data are expressed as the percentage of positive cell from the total cell population.…”

“…To confirm the antiproliferative effects of calyculin and the potential induction of apoptosis by this phosphatase inhibitor in the mixed-cell adenotonsillar cultures of OSA-derived tonsils, we performed flow cytometric analysis using bromodeoxyuridine and annexin V staining, respectively (13). Exposure of the cell cultures to 100 nM calyculin dramatically reduced cellular proliferation ( Figure 5A, control versus calyculin A in total cells: 8.87 6 0.35% vs. 3.06 6 0.72%, P , 0.001; control versus calyculin A in T cells: 22.4 6 1.78% vs. 9.8 6 0.61%, P , 0.001; control versus calyculin A in B cells: 7.56 6 0.56% vs. 1.78 6 0.57%, P , 0.001) and resulted in a significantly higher rate of programmed cell death ( Figure 5B, control vs. calyculin A in total cells: 45.5 6 2.5% vs. 72.4 6 3.40%, P , 0.001).…”

Current Treatment of Selected Pediatric Sleep Disorders

“…In in vitro cultures, leukotriene antagonists such as montelukast reduced adenotonsillar cellular proliferation rates, suggesting that targeted pharmacologic disruption of the leukotriene pathways may provide nonsurgical alternatives for treatment of OSA in children [38]. Corticosteroids were also shown to reduce in vitro cellular proliferation and the production of pro-inflammatory cytokines in a tonsil/adenoid mixed-cell culture system [39]. Small studies evaluating the effects of anti-inflammatory therapies in children with OSA have been reported for longer than a decade.…”