Cytokines in narcolepsy: A systematic review and meta-analysis.

ABSTRACT

BACKGROUND: Narcolepsy is a sleep disorder characterized by a loss of hypocretin neurons in the hypothalamus. Inflammation is proposed as a mechanism for neurodegeneration in narcolepsy. Numerous studies have investigated peripheral cytokine measures in narcoleptic patients, though the results are not conclusive. The current systematic review and meta-analysis aims to address the question of how do serum/plasma cytokine levels change in narcolepsy. METHODS: A systematic search of the literature to July 2019, was conducted to identify studies that measured cytokine levels in patients with narcolepsy, compared with those in controls without narcolepsy. RESULTS: Twelve studies were included in the meta-analysis: ten for interleukin (IL)-6, five for IL-8, three for IL-10, and ten for tumor necrosis factor alpha (TNF-α). Compared with controls, patients with narcolepsy had higher plasma levels of IL-6 (95% CI [0.22, 3.74]; P = 0.03) and TNF-α (95% CI [0.53, 4.18]; P = 0.01), while did not significantly differ in plasma IL-8 (95% CI [-1.64, 2.08]; P = 0.82) and IL-10 (95% CI [-1.29, 0.72]; P = 0.57) as well as serum IL-6 (95% CI [-1.48, 0.32], P = 0.21) and TNF-α (95% CI [-3.14, 0.19], P = 0.08) and CSF IL-8 (95% CI [-1.16, 0.41]; P = 0.35) levels. Patients with narcolepsy exhibited lower CSF IL-6 (95% CI [-0.66, 0.06]; P = 0.02) levels comparing with controls. CONCLUSIONS: Patients with narcolepsy had elevated plasma levels of IL-6 and TNF-α and lower levels of CSF IL-6 than non-narcoleptic controls. Our results support the role of inflammation in the pathophysiology of narcolepsy. However, plasma levels of IL-8 and IL-10, serum levels of IL-6 and TNF-α and CSF IL-8 did not significantly differ between patients and controls.