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Original Research: Sleep Disorders |

Substance P and Neurokinin 1 Receptors as Potential Therapeutic Targets in Children With OSASubstance P and Tonsil Proliferation in OSA

David Gozal, MD, FCCP; Jinkwan Kim, PhD; Rakesh Bhattacharjee, MD; Julie L. Goldman, MD; Leila Kheirandish-Gozal, MD
Author and Funding Information

From the Section of Sleep Medicine (Drs Gozal, Kim, Bhattacharjee, and Kheirandish-Gozal), Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL; and the Department of Surgery (Dr Goldman), Division of Otolaryngology, University of Louisville, Louisville, KY.

Correspondence to: Leila Kheirandish-Gozal, MD, Section of Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, 5841 S Maryland Ave/MC2117, Chicago, IL 60637-1470; e-mail: lgozal@peds.bsd.uchicago.edu


Funding/Support: This study was supported in part by the Herbert T. Abelson Endowed Chair in Pediatrics.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(5):1039-1045. doi:10.1378/chest.13-2026
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Background:  Increased substance P (SP) levels and abundant expression of neurokinin (NK) 1 receptor in adenotonsillar tissues of children with OSA but not recurrent tonsillar infection (RI) suggest that NK1 antagonists could be useful in treating OSA.

Methods:  The effects of SP and the NK1 antagonist GR-82334 were examined on mixed cell cultures prepared from dissociated tonsils harvested intraoperatively from children with OSA and RI. Proliferation was assessed by [3H]-thymidine or 5-ethynyl-2′-deoxyuridine incorporation, and inflammatory cytokine production (tumor necrosis factor [TNF]-α, IL-6, IL-1β) was assessed in supernatants by enzyme-linked immunosorbent assay.

Results:  SP elicited dose-dependent increases in tonsillar cell proliferation in mixed cell cultures from children with OSA but not with RI (P < .0001). The NK1 antagonist exhibited dose-dependent reductions in cellular proliferative rates in OSA-derived cell cultures but not in RI-derived mixed cell cultures (P < .00001). SP treatment was associated with increased TNF-α and IL-6 production, and GR-82334 abrogated SP effects, as well as reduced basal cytokine release (P < .0001).

Conclusions:  SP pathways appear to underlie intrinsic proliferative and inflammatory signaling pathways in tonsillar tissues from children with OSA but not with RI. Selective disruption of these pathways may provide nonsurgical alternatives for prevention and treatment of pediatric OSA.

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