Plasma Levels of Tumor Necrosis Factor α and Soluble Tumor Necrosis Factor Receptors in Patients With Narcolepsy

Himmerich, Hubertus; Beitinger, P. A.; Fulda, Stephany; Wehrle, R.; Linseisen, Jakob; Wolfram, G.; Himmerich, Stephanie; Gedrich, Kurt; Wetter, Thomas C.; Pollmächer, Thomas

doi:10.1001/archinte.166.16.1739

Cited by 53 publications

(33 citation statements)

References 39 publications

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“…Regarding TNF-a and IL-6, our data are consistent with previous findings by Okun et al (2004) and Vgontzas et al (1997). However, two other studies (Himmerich et al, 2006;Hinze-Selch et al, 1998) found no significant increases in TNF-a. Himmerich et al (2006) found increased sTNFR p75 levels in narcolepsy, but sTNFR p55 levels were not increased.…”

Section: Discussionsupporting

confidence: 92%

“…However, two other studies (Himmerich et al, 2006;Hinze-Selch et al, 1998) found no significant increases in TNF-a. Himmerich et al (2006) found increased sTNFR p75 levels in narcolepsy, but sTNFR p55 levels were not increased. The most likely reasons for these inconsistencies between the studies are the very subtle changes reported and the low numbers of patients investigated.…”

Section: Discussionmentioning

confidence: 87%

“…Moreover, abnormalities in numerous endocrine variables have been described, although the respective studies are somewhat inconsistent (Pollmächer et al, 2011) and subtle abnormalities in systemic immune parameters have been found, mainly changes in the levels of inflammatory cytokines. In particular, the systemic levels of tumour necrosis factor alpha (TNF-a) or its soluble receptors (sTNFR p55 and p75) have been found to be increased (Himmerich et al, 2006;Okun et al, 2004;Vgontzas et al, 1997). Inflammatory cytokines, such as TNF-a or interleukin 6 (IL-6), play a key role in linking the immune system to endocrine and metabolic networks.…”

Section: Introductionmentioning

confidence: 99%

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Hypothalamo–pituitary–adrenal axis, glucose metabolism and TNF‐α in narcolepsy

Maurovich-Horvat

Keckeis

Lattová

et al. 2014

Journal of Sleep Research

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SUMMARYNarcolepsy with cataplexy is caused by a deficiency in the production of hypocretin/orexin, which regulates sleep and wakefulness, and also influences appetite, neuroendocrine functions and metabolism. In this case-control study, 11 patients with narcolepsy with cataplexy and 11 healthy adults underwent an oral glucose tolerance test, and dexamethasone suppression/corticotropin-releasing hormone stimulation test. The average age of patients and controls was 35.1 AE 13.2 and 41.0 AE 2.9 years, respectively, body mass index was 28.1 AE 6.6 and 25.5 AE 4.7 kg m À2. We did not find evidence of a significantly increased prevalence of disturbed glucose tolerance in patients with narcolepsy. After hypothalamo-pituitary-adrenal axis suppression, the number of non-suppressors did not differ between the groups, indicating normal negative feedback sensitivity. The level of cortisol after dexamethasone suppression was significantly lower in patients with narcolepsy, suggesting a slight basal downregulation and/or a slightly increased negative feedback sensitivity of the major endocrine stress system in narcolepsy. Following corticotropin-releasing hormone stimulation, there were no significant differences in levels of adrenocorticotropic hormone or cortisol, and in adrenocortical responsivity to adrenocorticotropic hormone. Finally, patients with narcolepsy displayed significantly higher plasma levels of tumour necrosis factor alpha, soluble tumour necrosis factor receptor p55, soluble tumour necrosis factor receptor p75 and interleukin 6 after adjustment for body mass index. The present study confirms that narcolepsy by itself is not associated with disturbances of glucose metabolism, but goes along with a subtle dysregulation of inflammatory cytokine production. We also found that dynamic hypothalamo-pituitary-adrenal system response is not altered, whereas negative feedback to dexamethasone might be slightly enhanced. IN TROD UCTI ONNarcolepsy is a rare, chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations and sleep paralysis. Low cerebral spinal fluid hypocretin/orexin levels, caused by selective loss of hypocretin-producing neurons in the prefornical hypothalamus, due to possible autoimmune mechanisms, are reported in 95% of patients with narcolepsy with cataplexy (NC) (Baumann and Bassetti, 2005).In addition to their crucial role as regulators of sleep and wakefulness, hypocretin neurons have been shown to play an important role in energy homeostasis. For example, hypocretins increase food intake, and are involved in glucose metabolism and insulin sensitivity. Furthermore, they have a stimulatory role on the major stress system and can activate

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hypothalamo–pituitary–adrenal axis, glucose metabolism and TNF‐α in narcolepsy

Maurovich-Horvat

Keckeis

Lattová

et al. 2014

Journal of Sleep Research

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“…Subjects suffering from inflammation frequently exhibit tiredness or sleepiness mediated by the increased production of proinflammatory cytokines in the setting of ‘sickness behavior', which resembles depressive symptoms [4,7]. Narcolepsy, a disorder with increased daytime sleepiness, was found to be associated with specific markers of the HLA system and increased production of proinflammatory cytokines [21,42,43]. Cytokines not only influence wakefulness regulation, but their concentrations also change depending on sleep characteristics or following sleep deprivation [44,45,46].…”

Section: Discussionmentioning

confidence: 99%

“…Somnogenic effects may be further promoted by an impact on the HPA axis, including an increase in growth hormone-releasing hormone [5,17,18,19]. States of low-grade inflammation with upregulation of cytokine signaling feature in disorders in which excessive daytime sleepiness is commonly observed, such as metabolic syndrome [20], obstructive sleep apnea and HLA-DR2-positive narcolepsy [21,22]. Cytokine levels are further related to certain habits like daily napping and the extent of physical activity [10].…”

Section: Introductionmentioning

confidence: 99%

Impact of Serum Cytokine Levels on EEG-Measured Arousal Regulation in Patients with Major Depressive Disorder and Healthy Controls

et al. 2016

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Background: In major depressive disorder (MDD), findings include hyperstable regulation of brain arousal measured by electroencephalography (EEG) vigilance analysis and alterations in serum levels of cytokines. It is also known that cytokines affect sleep-wake regulation. This study investigated the relationship between cytokines and EEG vigilance in participants with MDD and nondepressed controls, and the influence of cytokines on differences in vigilance between the two groups. Methods: In 60 patients with MDD and 129 controls, 15-min resting-state EEG recordings were performed and vigilance was automatically assessed with the VIGALL 2.0 (Vigilance Algorithm Leipzig). Serum levels of the wakefulness-promoting cytokines interleukin (IL)-4, IL-10, IL-13 and somnogenic cytokines tumor necrosis factor-α, interferon-γ and IL-2 were measured prior to the EEG. Results: Summed wakefulness-promoting cytokines, but not somnogenic cytokines, were significantly associated with the time course of EEG vigilance in the MDD group only. In both groups, IL-13 was significantly associated with the course of EEG vigilance. In MDD compared to controls, a hyperstable EEG vigilance regulation was found, significant for group and group × time course interaction. After controlling for wakefulness-promoting cytokines, differences in vigilance regulation between groups remained significant. Conclusions: The present study demonstrated a relationship between wakefulness-promoting cytokines and objectively measured EEG vigilance as an indicator for brain arousal. Altered brain arousal regulation in MDD gives support for future evaluation of vigilance measures as a biomarker in MDD. Since interactions between cytokines and EEG vigilance only moderately differed between the groups and cytokine levels could not explain the group differences in EEG vigilance regulation, cytokines and brain arousal regulation are likely to be associated with MDD in independent ways.

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