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

• Published in: Psychopharmacology Vol. 233; no. 18; pp. 3429 - 3435
• Main Authors: Sharpley, Ann L., Cooper, Charlotte M., Williams, Clare, Godlewska, Beata R., Cowen, Philip J.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2016; Springer; Springer Nature B.V
• Subjects: Adult; Affect - drug effects; Biomedical and Life Sciences; Biomedicine; Clinical trials; Cross-Over Studies; Cytokines - drug effects; Cytokines - immunology; Depression - immunology; Depressive Disorder, Major - immunology; Dosage and administration; Double-Blind Method; Female; Healthy Volunteers; Humans; Inflammation - immunology; Interleukin-6 - immunology; Male; Neurosciences; Original Investigation; Patient outcomes; Pharmacology/Toxicology; Placebo effect; Polysomnography; Psychiatry; Sleep; Sleep - drug effects; Typhoid; Typhoid vaccines; Typhoid-Paratyphoid Vaccines - pharmacology; Vaccines; Young Adult; Typhoid vaccine; Sleep continuity disturbances; Depression; Inflammation; Healthy participants; Interleukin-6
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-016-4381-z

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