Original Article

Th17 Cell Related Cytokine Profiles in Narcolepsy and Other Types of Excessive Daytime Sleepiness


Background and Objective: Narcolepsy is a chronic neurological disorder caused by loss of hypocretin (Hcrt) neurons. Both genetic and environmental factors play an important role for the development of narcolepsy. The mechanism of Hcrt loss in narcolepsy is elusive; however, an autoimmune mediated destruction of Hcrt neurons is suspected. The purpose of this study was to assess Th17 related cytokines: interleukin-6 (IL-6), IL-17, IL-23, and transforming growth factor beta (TGF-β) in the pathophysiology of narcolepsy and other types of excessive daytime sleepiness (EDS).
Materials and Methods: A total of 15 narcoleptic patients, 35 other patients with EDS and 48 age and sex matched healthy subjects were enrolled in this case-control study. Serum IL-6, IL-17, IL-23, and TGF-β levels were measured using sandwich enzyme-linked immunosorbent assay.
Results: There was no significant difference in IL-6 (P = 0.0618) and IL-23 (P = 0.7717) level among participants with narcolepsy, other patients with EDS and controls, whereas TGF-β was significantly decreased in the ones with narcolepsy and other EDS compared to healthy controls (P = 0.0039).
Conclusion: Decreased level of TGF-β in narcolepsy and other patients with EDS indicates a clue for the presence of dysregulation of inflammatory cascades in these patients. This study sheds a new insight on the pathophysiology of narcolepsy.

Mahlios J, De la Herran-Arita AK, Mignot E. The autoimmune basis of narcolepsy. Curr OpinNeurobiol 2013; 23: 767-73.

Partinen M, Kornum BR, Plazzi G, et al. Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination. Lancet Neurol 2014;13: 600-13.

Bergman P, Adori C, Vas S, et al. Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns. Proc Natl Acad Sci U S A 2014; 111: E3735-E3744.

Singh AK, Mahlios J, Mignot E. Genetic association, seasonal infections and autoimmune basis of narcolepsy. J Autoimmun 2013; 43: 26-31.

Partinen M, Saarenpaa-Heikkila O, Ilveskoski I, et al. Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. PLoS One 2012; 7: e33723.

Han F. Sleepiness that cannot be overcome:narcolepsy and cataplexy. Respirology 2012; 17: 1157-65.

Han F, Faraco J, Dong XS, et al. Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic. PLoS Genet 2013; 9: e1003880.

Kornum BR, Faraco J, Mignot E. Narcolepsy with hypocretin/orexin deficiency, infections and autoimmunity of the brain. Curr Opin Neurobiol 2011;21: 897-903.

Kumar S, Sagili H. Etiopathogenesis and neurobiology of narcolepsy: a review. J Clin Diagn Res 2014; 8: 190-5.

Bayard S, Croisier Langenier M, Cochen De Cock V, et al. Executive control of attention in narcolepsy. PLoS One 2012; 7: e33525.

Holm A, Bang-Berthelsen CH, Knudsen S, et al. miRNA profiles in plasma from patients with sleep disorders reveal dysregulation of miRNAs in narcolepsy and other central hypersomnias. Sleep 2014; 37: 1525-33.

Okun ML, Giese S, Lin L, et al. Exploring the cytokine and endocrine involvement in narcolepsy. Brain Behav Immun 2004; 18: 326-32.

Santos Coelho FM, de Sousa HP, Alves GR, et al. TNF and IL-6 levels in narcoleptic patients. Einstein 2006; 4: 327-30.

Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 1997; 82: 1313-6.

Zhan S, Cai GQ, Zheng A, et al. Tumor necrosis factor-alpha regulates the Hypocretin system via mRNA degradation and ubiquitination. Biochim Biophys Acta 2011; 1812: 565-71.

Ahmed SS, Schur PH, MacDonald NE, et al. Narcolepsy, 2009 A(H1N1) pandemic influenza, and pandemic influenza vaccinations: what is known and unknown about the neurological disorder, the role for autoimmunity, and vaccine adjuvants. J Autoimmun 2014; 50: 1-11.

Bardage C, Persson I, Ortqvist A, et al. Neurological and autoimmune disorders after vaccination against pandemic influenza A (H1N1) with a monovalent adjuvanted vaccine: population based cohort study in Stockholm, Sweden. BMJ 2011;343: d5956.

Nishino S, Ripley B, Overeem S, et al.Hypocretin (orexin) deficiency in human narcolepsy. Lancet 2000; 355: 39-40.

Kapsimalis F, Basta M, Varouchakis G, et al. Cytokines and pathological sleep. Sleep Med 2008; 9:603-14.

Zhou L, Lopes JE, Chong MM, et al. TGF-beta- induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 2008; 453:236-40.

IssueVol 1 No 2 (2016): Spring QRcode
SectionOriginal Article(s)
Narcolepsy Cataplexy Hypocretin IL-6 TGF-β IL-17 IL-23

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How to Cite
Debebe D, Sadeghniat-Haghighi K, Shakiba Y, Rahimi Golkhandan A, Izad M. Th17 Cell Related Cytokine Profiles in Narcolepsy and Other Types of Excessive Daytime Sleepiness. J Sleep Sci. 1(2):44-50.