Non-motor symptoms in patients with Parkinson's disease - correlations with inflammatory cytokines in serum

PLoS One. 2012;7(10):e47387. doi: 10.1371/journal.pone.0047387. Epub 2012 Oct 17.

Abstract

Background: Parkinson'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 materials: We 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.

Results: IL-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.

Discussion: We 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • C-Reactive Protein
  • Case-Control Studies
  • Confounding Factors, Epidemiologic
  • Cytokines / blood*
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Motor Activity / physiology*
  • Parkinson Disease / blood*
  • Parkinson Disease / physiopathology*
  • Receptors, Interleukin-2 / blood
  • Regression Analysis
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Cytokines
  • Inflammation Mediators
  • Interleukin-6
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein

Grants and funding

This study was performed with the support of the Swedish Research Council grants, the Sjöbring Foundation, OM Persson Foundation and the province of Scania state grants (ALF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.