The Effect Of Acute Stress On Salivary Markers Of Inflammation: A Systematic Review And Meta-Analysis

Background: Salivary biomarkers of inflammation are increasingly used in stress research. This systematic review and meta-analysis provides a quantitative summary of changes in salivary inflammatory markers in response to acute stress. Method: The review included 1558 participants (42 unique samples, 33 studies) obtained through electronic databases (PubMed, PsycINFO, Embase), reference treeing, and articles identified by a 2015 review on a similar topic. To be eligible, articles had to be quantitative and assess change in at least one biomarker of salivary inflammation in response to acute stress in adults. The primary outcome was magnitude of change in inflammatory biomarkers (Cohens d for repeated measures [d(av)]). Results: Measures of salivary inflammation included: C-reactive protein (CRP), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-21, interferon (IFN)-alpha, IFN-gamma, and tumor necrosis factor (TNF)-alpha. Cytokines IL-6 (k = 26, d(av) = 0.27), IL-10 (k = 11, d(av) = 0.34), TNF-alpha (k = 10, d(av) = 0.57), and IFN-gamma (k = 6, d(av) = 0.28) significantly increased in response to stress. Post hoc sensitivity analyses revealed that IL-1 beta (k = 19, d(av) = 0.16) and IL-8 (k = 7, d(av) = 0.30) also increased from pre- to post-stress, but findings with IFN-gamma did not hold after removing one outlier study. Examination of moderators suggested that study methodology and sample demographics moderated some associations. Conclusions: This meta-analysis revealed that certain salivary inflammatory cytokines increase in response to acute stress. Significant heterogeneity in results and moderator analyses suggest need for standardization of research protocols. Directions for future research are discussed.