Effects of typhoid vaccine on inflammation and sleep in healthy participants: a double-blind, placebo-controlled, crossover study

Ann L Sharpley, Charlotte M Cooper, Clare Williams, Beata R Godlewska, Philip J Cowen, Ann L Sharpley, Charlotte M Cooper, Clare Williams, Beata R Godlewska, Philip J Cowen

Abstract

Rationale: An increasing body of evidence links the occurrence of sleep continuity disturbances with increased inflammation and both sleep disturbances and inflammation are associated with clinical depression. Typhoid vaccination results in a mild inflammatory response that significantly increases levels of the proinflammatory cytokine, interleukin (IL)-6.

Objectives: The present exploratory study aimed to enhance our understanding of the link between inflammation, sleep and depression by examining the effects of typhoid vaccine on the sleep polysomnogram.

Methods: We studied the effects of a single injection of typhoid polysaccharide vaccine and placebo (saline solution) on sleep in 16 healthy male and female participants aged 20-38 years, sleeping at home in a randomized, double-blind, balanced order, crossover design. Subjective measures of mood, sleep and adverse effects were elicited and plasma samples analysed for IL-6 levels.

Results: IL-6 levels (in picogramme per millilitre) significantly increased 2 h post vaccine compared to placebo (0.90 vs 0.53, p = 0.026, r = 0.55). Relative to placebo, typhoid vaccination produced significant impairment in several measures of sleep continuity. Total sleep time (in minute) (426.1 vs 410.7, p = 0.005, r = 0.62) and sleep efficiency percent (94.3 vs 91.5, p = 0.007, r = 0.65) were decreased; with increases in wake after sleep onset (in minute) (25.5 vs 38.8, p = 0.007,r = 0.65), total wake (in minute) (34.9 vs 50.3, p = 0.005,r = 0.67), sleep stage transitions (155.9 vs 173.1, p = 0.026, r = 0.56), number of awakenings (27.2 vs 36.1, p = 0.007, r = 0.64) and awakening index (3.8 vs 5.3, p = 0.005, r = 0.67) (means, significance level and effect size).

Conclusions: Inflammatory mechanisms may underlie the impairment in sleep efficiency which is a hallmark of major depression. Because impaired sleep is also a predictor of major depression, there may be a role for suitable anti-inflammatory approaches in strategies designed to prevent the onset of depression. ClinicalTrials.gov ( http://www.clinicaltrials.gov ): NCT02628054.

Keywords: Depression; Healthy participants; Inflammation; Interleukin-6; Sleep continuity disturbances; Typhoid vaccine.

Figures

Fig. 1
Fig. 1
Effect of typhoid vaccine and placebo on wake after sleep onset (minutes) n = 15. Paired samples t test mean = p = 0.007
Fig. 2
Fig. 2
Effect of typhoid vaccine and placebo on plasma IL-6 (in picogramme per millilitre) levels. n = 15 paired t test P = 0.026

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