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. 2023 Jan;35(1):117-126.
doi: 10.1007/s40520-022-02292-9. Epub 2022 Nov 1.

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

Georgia M Parkin  1   2 , Soyun Kim  3 , Abanoub Mikhail  3 , Rond Malhas  4 , Liv McMillan  3 , Martina Hollearn  3 , Douglas A Granger  2   5 , Mark Mapstone  4 , Michael A Yassa  3 , Elizabeth A Thomas  6   7
Affiliations

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

Georgia M Parkin et al. Aging Clin Exp Res. 2023 Jan.

Abstract

Background: Inflammatory responses play key roles in the development and progression of many pathological conditions, including neurodegenerative diseases. Accurate quantification of inflammatory factors in saliva would be highly advantageous, given its convenience and non-invasive nature, especially in elderly populations.

Methods: In this study, we measured levels of 10 cytokines, and the pro-inflammatory factor, YKL-40, in plasma and saliva samples from a cohort of nondemented older adults (n = 71; 62% female; 70.3 ± 6.4 years) using sensitive electrochemiluminescence-based immunoassays.

Results: We found that the mean levels of all cytokines were higher in saliva compared to plasma and that strong sex differences were observed for both saliva and plasma cytokines in this population. Comparing each cytokine between the two biofluids, we found that levels of interferon-gamma (IFNγ), interleukin (IL)-6 and tumor necrosis factor-alpha (TNFα) 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-1β, IL-10, IL-8, IL12p70 and IL-13.

Conclusions: These findings show that inflammatory markers in saliva are associated with those found in circulation, suggesting shared inflammatory mechanisms between these two fluids. The higher levels of cytokines measured in saliva suggest that it might represent a better peripheral fluid to gauge inflammatory processes. Finally, our findings of robust sex differences in several salivary cytokines could have important implications for their potential use as disease biomarkers in the elderly and might be related to sex differences in the prevalence of age-related conditions.

Keywords: Biomarker; Cytokine; Disease; Peripheral; Saliva.

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Conflict of interest statement

Doug Granger is founder and majority equity holder of Salimetrics LLC and Salivabio LLC. He serves as the Chief Scientific and Strategy Advisor at these companies. These relationships are managed by the policies of the committees on conflict of interest at the Johns Hopkins University School of Medicine and University of California at Irvine. Mark Mapstone is an inventor on patents assigned to Georgetown University, the University of Rochester and the National Institutes of Health. The terms of this arrangement have been reviewed and approved by the University of California, Irvine in accordance with its conflict of interest policies. Remaining authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1
Sex effects of salivary (A) and plasma (B) cytokine levels. Proinflammatory markers (TNFα, IL1β, IL-2, IL-6, IL-8, IL-12p70, IFNγ, and YKL-40) and anti-inflammatory markers (IL-4, IL-10, and IL-13) were measured in plasma and saliva samples from a cohort of cognitively normal elderly participants (n = 71; 62% female; mean age 70.3 ± 6.4 years). Plasma levels of IL-1b, IL-2, IL-4, IL-12p70, and IL-13 were below detection in > 30% of samples, hence were not included in the analyses. Significant differences were determined using Student’s t test on Log-transformed values: *p < 0.05; **p < 0.01
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References

    1. Chauhan P, Nair A, Patidar A, et al. A primer on cytokines. Cytokine. 2021;145:155458. doi: 10.1016/j.cyto.2021.155458. - DOI - PubMed
    1. Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007;45:27–37. doi: 10.1097/AIA.0b013e318034194e. - DOI - PMC - PubMed
    1. Byrne ML, O’Brien-Simpson NM, Reynolds EC, et al. Acute phase protein and cytokine levels in serum and saliva: a comparison of detectable levels and correlations in a depressed and healthy adolescent sample. Brain Behav Immun. 2013;34:164–75. doi: 10.1016/j.bbi.2013.08.010. - DOI - PubMed
    1. Browne RW, Kantarci A, LaMonte MJ, et al. Performance of multiplex cytokine assays in serum and saliva among community-dwelling postmenopausal women. PLoS One. 2013;8:e59498. doi: 10.1371/journal.pone.0059498. - DOI - PMC - PubMed
    1. Riis JL, Out D, Dorn LD, et al. Salivary cytokines in healthy adolescent girls: intercorrelations, stability, and associations with serum cytokines, age, and pubertal stage. Dev Psychobiol. 2014;56:797–811. doi: 10.1002/dev.21149. - DOI - PMC - PubMed