Cytokines in narcolepsy: A systematic review and meta-analysis

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.

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.

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.

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.