title: Cerebrospinal fluid and serum cytokine profiles in narcolepsy with cataplexy: a case-control study.
abstract: Recent advances in the identification of susceptibility genes and environmental exposures provide strong support that narcolepsy-cataplexy is an immune-mediated disease. Only few serum cytokine studies with controversial results were performed in narcolepsy and none in the cerebrospinal fluid. We measured a panel of 12 cytokines by a proteomic approach in the serum of 35 patients with narcolepsy-cataplexy compared to 156 healthy controls, and in the cerebrospinal fluid of 34 patients with narcolepsy-cataplexy compared to 17 non-narcoleptic patients; and analyzed the effect of age, duration and severity of disease on the cytokine levels. After multiple adjustments we reported lower serum IL-2, IL-8, TNF-α, MCP-1 and EGF levels, and a tendency for higher IL-4 level in narcolepsy compared to controls. Significant differences were only found for IL-4 in cerebrospinal fluid, being higher in narcolepsy. Positive correlations were found in serum between IL-4, daytime sleepiness, and cataplexy frequency. The expression of some pro-inflammatory cytokines (MCP-1, VEGF, EGF, IL2, IL-1β, IFN-γ) in either serum or CSF was negatively correlated with disease severity and duration. No correlation was found for any specific cytokine in 18 of the patients with narcolepsy with peripheral and central samples collected the same day. Significant decreased pro/anti-inflammatory cytokine profiles were found at peripheral and central levels in narcolepsy, together with a T helper 2/Th1 serum cytokine secretion imbalance. To conclude, we showed some evidence for alterations in the cytokine profile in patients with narcolepsy-cataplexy compared to controls at peripheral and central levels, with the potential role of IL-4 and significant Th1/2 imbalance in the pathophysiology of narcolepsy.
authors.affiliation: CHU Montpellier, Service de Neurologie, Unité des Troubles du Sommeil, Hôpital Gui-de-Chauliac, Montpellier, France; National Reference Network for Orphan Diseases (Narcolepsy, Idiopathic Hypersomnia and Kleine Levin Syndrome), France; Inserm, U1061, F-34000 Montpellier, France; Université Montpellier 1, F-34000 Montpellier, France; Pôle Gérontologie CHU Montpellier, M2H Euromov, Université Montpellier 1, France. Electronic address: ydauvilliers@yahoo.fr.
authors.forename: Yves
authors.initials: Y
authors.lastname: Dauvilliers
authors.affiliation: Inserm, U1061, F-34000 Montpellier, France; Université Montpellier 1, F-34000 Montpellier, France; Pôle Gérontologie CHU Montpellier, M2H Euromov, Université Montpellier 1, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Jaussent
authors.affiliation: National Reference Network for Orphan Diseases (Narcolepsy, Idiopathic Hypersomnia and Kleine Levin Syndrome), France; Pediatric Sleep Disorder Centre, CHU Robert-Debré, AP-HP, Paris, France; Pôle Gérontologie CHU Montpellier, M2H Euromov, Université Montpellier 1, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Lecendreux
authors.affiliation: CHU Montpellier, Service de Neurologie, Unité des Troubles du Sommeil, Hôpital Gui-de-Chauliac, Montpellier, France; National Reference Network for Orphan Diseases (Narcolepsy, Idiopathic Hypersomnia and Kleine Levin Syndrome), France; Pôle Gérontologie CHU Montpellier, M2H Euromov, Université Montpellier 1, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Scholz
authors.affiliation: CHU Montpellier, Service de Neurologie, Unité des Troubles du Sommeil, Hôpital Gui-de-Chauliac, Montpellier, France; National Reference Network for Orphan Diseases (Narcolepsy, Idiopathic Hypersomnia and Kleine Levin Syndrome), France; Inserm, U1061, F-34000 Montpellier, France; Université Montpellier 1, F-34000 Montpellier, France; Pôle Gérontologie CHU Montpellier, M2H Euromov, Université Montpellier 1, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Bayard
authors.affiliation: Université Montpellier 1, F-34000 Montpellier, France; Laboratoire de Biochimie, F-34000 CHRU Montpellier, France; Pôle Gérontologie CHU Montpellier, M2H Euromov, Université Montpellier 1, France.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Cristol
authors.affiliation: Université Montpellier 1, F-34000 Montpellier, France; Laboratoire de Biochimie, F-34000 CHRU Montpellier, France; Pôle Gérontologie CHU Montpellier, M2H Euromov, Université Montpellier 1, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Blain
authors.affiliation: Inserm, U1061, F-34000 Montpellier, France; Laboratoire de Biochimie, F-34000 CHRU Montpellier, France; Pôle Gérontologie CHU Montpellier, M2H Euromov, Université Montpellier 1, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Dupuy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002385:Cataplexy / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications / Q000378:metabolism*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: Autoimmunity; Cataplexy; Cytokine; Hypocretin; Narcolepsy; Sleep