Salivary Inflammatory Molecules as Biomarkers of Sleep Alterations: A Scoping Review

Abstract

Poor sleep quality and sleep disorders are the most common problems in people, affecting health-related quality of life. Various studies show an association between sleep disorders and altered levels of stress hormones and inflammatory cytokines measured in saliva. The main objective of this article is to provide an analysis of the current evidence related to changes in inflammatory markers in the saliva and their associations with sleep quality measurement (both objective and subjective methods) in healthy subjects and in sleep-related disorders. To that end, a scoping review was carried out, following the PRISMA criteria in the bibliographic search in several databases: PubMed, EBSCO, and SCOPUS. Eleven of the articles are from the adult population and two from the child-youth population. They mainly measure the relationship between sleep and interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα) alpha, as well as other inflammatory markers such as myeloperoxidase (MPO) and prostaglandin-endoperoxide synthase 2. An analysis shows the relationship between these salivary biomarkers and sleep quality, especially in the case of IL-6 in both healthy subjects and several pathologies associated with sleep-disorders. The results for TNFα and IL-1β measurements are still inconclusive and the difference with IL-6 was assessed. Two studies reported interventions that result in sleep improvement and are accompanied by the normalization of inflammatory changes detected in the saliva. As it is an easy-to-apply and non-invasive method, the measurement of salivary cytokines can be very useful in chronobiology studies. Further studies are required to determine the sensitivity of salivary inflammatory markers in monitoring biological rhythms and acting as biomarkers in the detection of sleep disorders and sleep interventions.

Salivary IL-6 Concentration Is Associated with Frailty Syndrome in Older Individuals

“…Some studies have obtained results indicating that salivary IL-6 is highly correlated with blood levels [ 70 ]. Saliva testing can therefore be a non-invasive tool for frailty diagnosis, without the sampling technique entailing added stress for the patient which implies changes in levels which could occur as a result of the stress associated with drawing blood [ 35 ], and it is inexpensive, can be conducted in ecological contexts across time, and at multiple moments throughout the day [ 27 ]. Saliva tests could therefore be used for the diagnosis and to indicate the existence or the risk of developing a disease, as well as the response to a particular therapy.…”

“…A biomarker is a measurable nano-protein, which is used to predict a biological state [ 32 ]. Some studies have analyzed salivary IL-6 levels in patients not only with common oral pathologies [ 33 ], but also in systemic diseases such as polycystic ovary syndrome [ 34 ], bladder pain syndrome sleep disorders [ 35 ], in sepsis [ 29 ], Huntington’s disease [ 36 ], diabetes [ 37 ], in stroke [ 38 ], Hashimoto’s disease [ 39 ], and inflammatory diseases [ 40 ]. However, the association between salivary IL-6 levels in patients with frail syndrome is unknown.…”

Inflammatory Biomarkers for Children with Sleep Disorders: A Review

“…Repetitive hypoxia and reoxygenation associated with OSA are believed to cause oxidative stress 13 14 and the production of reactive oxygen species (ROS), which may play a role in the activation of an inflammatory response in OSA patients. 15…”

“…Ibáñez-del Valle et al analyzed the alterations in salivary inflammatory biomarkers and their relationships with evaluation of sleep quality parameters. 13 Eleven articles were pertaining to adults while only two focused on children/youth population. They primarily assessed the link between sleep and IL-1, IL-6, TNF-α, and some other inflammatory markers such as myeloperoxidase (MPO) and prostaglandin-endoperoxide synthase 2.…”

“…However, their review found only two studies related to children. 13 Therefore, there is a lacuna of knowledge regarding inflammatory biomarkers for the evaluation of sleep disorders in children. In the present review, we sought to examine the existing literature regarding inflammatory biomarkers among children with sleep disorders.…”