Levels of Interleukin-6 in Saliva, but Not Plasma, Correlate with Clinical Metrics in Huntington’s Disease Patients and Healthy Control Subjects

Abstract

Growing evidence suggests that inflammatory responses, in both the brain and peripheral tissues, contribute to disease pathology in Huntington’s disease (HD), an inherited, progressive neurodegenerative disorder typically affecting adults in their 30–40 s. Hence, studies of inflammation-related markers in peripheral fluids might be useful to better characterize disease features. In this study, we measured levels of C-reactive protein (CRP), Interleukin-6 (IL-6), interleukin 1 beta (IL-1B), and alpha-amylase (AA) in saliva and plasma from n = 125 subjects, including n = 37 manifest HD patients, n = 36 premanifest patients, and n = 52 healthy controls, using immunoassays. We found increases in salivary levels of IL-6, IL-1B and CRP across different disease groups and increased levels of IL-6 in the plasma of HD patients as compared to premanifest patients and controls. The levels of salivary IL-6 were significantly correlated with each of the other salivary markers, as well as with IL-6 levels measured in plasma. Further, salivary IL-6 and IL-1B levels were significantly positively correlated with Total Motor Score (TMS) and chorea scores and negatively correlated with Total Functional Capacity (TFC) in HD patients, whereby in healthy control subjects, IL-6 was significantly negatively correlated with Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities test (SDM). Interestingly, the plasma levels of IL-6 did not show similar correlations to any clinical measures in either HD or control subjects. These findings suggest that salivary IL-6 is particularly relevant as a potential non-invasive biomarker for HD symptoms. The advent of an effective, dependable salivary biomarker would meet the urgent need for a less invasive means of identifying and monitoring HD disease progression.

Human Saliva as a Diagnostic Specimen for Early Detection of Inflammatory Biomarkers by Real-Time RT-PCR

“…Bloom et al suggest that salivary IL-6 is a potential non-invasive biomarker for Huntington's disease (HD) symptoms, which is a progressive and inherited neurodegenerative disorder typically affecting adults of age 30-40 [9]. The advent of an effective and reliable salivary biomarker would undoubtedly meet the urgent need for a noninvasive means of detecting and monitoring HD disease progression [9].…”

“…Bloom et al suggest that salivary IL-6 is a potential non-invasive biomarker for Huntington's disease (HD) symptoms, which is a progressive and inherited neurodegenerative disorder typically affecting adults of age 30-40 [9]. The advent of an effective and reliable salivary biomarker would undoubtedly meet the urgent need for a noninvasive means of detecting and monitoring HD disease progression [9]. Another recent report states that the best marker combination which includes inflammatory cytokines that differentiated active TB (tuberculosis) from healthy controls were fractalkine + IP-10 + IL-1α + VEGF in saliva [12].…”

What, When and How to Measure—Peripheral Biomarkers in Therapy of Huntington’s Disease

“…The background of HD pathophysiology is also being described by research concerning oxidative stress. Recent studies indicate that oxidative damage, along with mitochondrial dysfunction and impairment in the electron transport chain, plays a significant role in neurodegenerative processes [ 72 , 73 ]. However, despite a growing number of studies that indicate the importance of oxidative damage in HD, identification of the main pathways of disease pathogenesis associated with oxidative stress has not been fully explained.…”

“…However, despite a growing number of studies that indicate the importance of oxidative damage in HD, identification of the main pathways of disease pathogenesis associated with oxidative stress has not been fully explained. In HD, this effect is of particular importance in the progression of the disease in later stages, contributing to the worsening of the pathological condition [ 72 ]. Increased oxidative stress along with oxidative DNA damage has been reported in the peripheral blood of HD patients [ 74 , 75 ].…”

Biomarkers in Rare Diseases

“…Another study investigating inflammatory changes as a relevant biomarker of disease is that of Corey-Bloom and co-workers [ 11 ]. This group examined inflammation markers in the saliva and plasma of patients with Huntington’s disease, an inherited, progressive neurodegenerative disorder.…”