4.6 Article

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

Journal

PEDIATRIC RESEARCH
Volume 66, Issue 4, Pages 423-428

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1203/PDR.0b013e3181b453e3

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Funding

  1. National Institutes of Health [HL-065270, HL-086662, HL-083075]
  2. Commonwealth of Kentucky Research Challenge for Excellence Trust Fund
  3. Children's Foundation Endowment for Sleep Research
  4. Merck Company
  5. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U01HL083075, R01HL065270, R01HL086662] Funding Source: NIH RePORTER

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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 < 0.01), with CD3(+), CD4(+), and CD8(+) cell proliferation being higher in OSA (p < 0.05). Moreover, proinflammatory cytokines, Such as TNF-alpha, IL-6, and IL-1 alpha, 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) < 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. (Pediatr Res 66: 423-428, 2009)

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