Increased Cellular Proliferation and Inflammatory Cytokines in Tonsils Derived From Children With Obstructive Sleep Apnea

Abstract

Adenotonsillar hypertrophy is the major pathophysiological mechanism underlying obstructive sleep apnea (OSA) and recurrent tonsillitis (RI) in children. The increased expression of various mediators of the inflammatory response in tonsils of patients with OSA prompted our hypothesis that the enhanced local and systemic inflammation in children with OSA would promote tonsillar proliferation. Mixed cell cultures from tonsils recovered during adenotonsillectomy in children with OSA and RI were established, and proliferative rates were assessed. Cells were also cultured to determine the levels of proinflammatory cytokines and antioxidant protein levels and mRNA expression. Global cell proliferative rates from OSA tonsils were significantly higher than RI (p Ͻ 0.01), with CD3 ϩ , CD4 ϩ , and CD8 ϩ cell proliferation being higher in OSA (p Ͻ 0.05). Moreover, proinflammatory cytokines, such as TNF-␣, IL-6, and IL-1␣, were highly expressed in OSA-derived tonsils. Furthermore, thioredoxin (TRX), an antioxidant protein, was also highly expressed in OSA tonsils at the mRNA and protein levels (p Ͻ 0.01). Thus, T cells are in a highly proliferative state in the tonsils of children with OSA and are associated with increased production of proinflammatory cytokines and TRX, when compared with children with RI. (1). In a series of previous studies from our and other laboratories, it has become apparent that children with OSA are at increased risk for a vast array of morbidities, principally affecting the CNS and cardiovascular systems (2-9). Adenotonsillar hypertrophy has been recognized as the major pathophysiological contributor of OSA in children (10), and it plays an important role as well in recurrent tonsillitis (RI) (11). Consequently, adenotonsillectomy (T&A) is currently the first line of treatment for children with these conditions (12,13). However, the exact mechanisms underlying follicular lymphoid proliferation and hyperplasia remain extremely poorly understood. In adults, there are several lines of evidence, suggesting that both local upper airway and systemic inflammation are implicated in the pathophysiology of this a priori mechanical dysfunction of the upper airway. For example, the number of immune cells is substantially increased in the upper airway mucosa and the muscle of adults with OSA (14). Similar increases in regional and systemic inflammatory markers have also been reported in children with OSA (15-17). In addition, increased expression of mediators of the inflammatory response, such as cysteinyl leukotrienes and glucocorticoid receptors, is consistently found in tonsillar tissues of children with OSA (18 -20). Therefore, we hypothesized that cellular proliferation of tonsillar tissues in children with OSA would differ from that of children with RI, possibly reflecting different pathologic mechanisms and cell type involvement leading to the enlargement of upper airway lymphoid tissue in these two conditions. METHODS Subjects. The study was approved by the University of Louisville HumanRese...

CD4+T-lymphocyte subsets in nonobese children with obstructive sleep apnea syndrome

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

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