Non-Motor Symptoms in Patients with Parkinson’s Disease – Correlations with Inflammatory Cytokines in Serum

Eli Kaufman,Lena Brundin,Yulia Surova,Oskar Hansson,Sara Hall,John Duda,Daniel Lindqvist

doi:10.1371/journal.pone.0047387

Abstract

BackgroundParkinson’s Disease (PD) is the second most common neurodegenerative disorder of the central nervous system. Motor symptoms are the focus of pharmacotherapy, yet non-motor features of the disease (e.g. fatigue, mood disturbances, sleep disturbances and symptoms of anxiety) are both common and disabling for the patient. The pathophysiological mechanisms behind the non-motor symptoms in PD are yet to be untangled. The main objective of this study was to investigate associations between pro-inflammatory substances and non-motor symptoms in patients with PD.Methods and MaterialsWe measured C-reactive protein, interleukin (IL)-6, soluble IL-2 receptor (sIL-2R) and tumor necrosis factor-α (TNF-α) in blood samples from PD patients (n = 86) and healthy controls (n = 40). Symptoms of fatigue, depression, anxiety and sleeping difficulties were assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT), the Hospital Anxiety and Depression Scale (HAD), and the Scales for Outcome in PD-Sleep Scale respectively.ResultsIL-6 was significantly higher in PD patients than in healthy controls. Compared to healthy controls, PD patients displayed significantly higher mean scores on HAD and lower scores on FACIT, thus indicating more severe symptoms as measured with these scales. Within the PD sample, high levels of both sIL-2R and TNF-α were significantly associated with more severe symptoms assessed by means of FACIT and HAD (depression and anxiety subscales). SIL-2-R levels were able to significantly predict FACIT and HAD scores after the effects of age, gender, anti-parkinsonian medications, and severity of motor symptoms were controlled for.DiscussionWe suggest that non-motor symptoms in PD patients, such as fatigue and depressive symptoms, might be generated via inflammatory mechanisms. This knowledge might contribute to the development of novel treatment options in PD, specifically targeting non-motor symptoms.

Highlights

Parkinson’s Disease (PD) is a chronic, neurodegenerative disease affecting approximately 2% of the population over the age of 60 and 4% of those over the age of 80 [1]
IL-6 was significantly higher in PD patients than in healthy controls
Within the PD sample, high levels of both soluble interleukin-2 receptor (sIL-2R) and tumor necrosis factor alpha (TNF-a) were significantly associated with more severe symptoms assessed by means of FACIT and Hospital Anxiety and Depression Scale (HAD)

Summary

Introduction

Parkinson’s Disease (PD) is a chronic, neurodegenerative disease affecting approximately 2% of the population over the age of 60 and 4% of those over the age of 80 [1]. Peripheral blood monocytes isolated from PD patients produce larger amounts of several cytokines, including tumor necrosis factor alpha (TNF-a), than healthy controls - indicating that the elevated serum levels of cytokines are symptoms of immunological dysregulation, rather than just secondary to the dopaminergic cell degeneration [14]. Some of these signs are demonstrable in depressed, non-PD patients.

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