Associations between saliva and plasma cytokines and YKL-40 in cognitively-normal, older adults

Abstract

Abstract Inflammatory responses play key roles in the development and progression of many pathological conditions, including neurodegenerative conditions. Accurate quantification of inflammatory factors in saliva would be highly advantageous, given its convenience and non-invasive nature, enabling use as biomarkers for disease processes especially in older adults. However, few studies have attempted to validate salivary assays by directly comparing cytokine levels in blood and saliva samples the same individuals. In this study, we measured levels of 10 cytokines, interferon gamma (IFNg), interleukin (IL)-1 beta (IL-1b), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13 and tumor necrosis factor alpha (TNFa), as well as the inflammatory glycoprotein, YKL-40, in blood and saliva samples from a cohort of nondemented older adults (n = 71; 62% female; mean age 70.3 +/- 6.4 yrs; ) using sensitive electrochemiluminescence-based immunoassays. We found that the mean levels of all cytokines were higher in saliva compared to plasma, and specifically that levels of IL-1b, IL-2, IL-4, IL-12p70 and IL-13 in plasma were below the instrument detection limit for more than 50% of the subjects. We found strong sex differences in both saliva and plasma cytokines, with levels of several salivary cytokines, as well as YKL-40, showing higher concentrations in males compared to females. Comparing each cytokine between the two biofluids, we found that levels of IFNg, IL-6 and TNFa in blood were significantly correlated with their respective levels in saliva. We further observed that levels of these cytokines in blood were significantly correlated with additional cytokines in saliva, including IL-1b, IL-10, IL-8, IL12p70 and IL-13. These findings show that inflammatory markers in saliva are associated with those found in circulation, suggesting that inflammatory mechanisms between these two fluids are, at least to some extent, related. Consistent with prior work, several salivary markers were more likely to surpass the detection threshold than plasma markers, suggesting that salivary assays may, at least in some cases, be more useful for detecting physiological changes. Further our findings of robust sex differences in several salivary cytokines could have important implications for their potential use as health or disease biomarkers.