Plasma IL-6 and IL-17A Correlate with Severity of Motor and Non-Motor Symptoms in Parkinson’s Disease

Abstract

The nature of the inflammatory response in Parkinson's disease (PD) remains to be better understood. Here, we used highly sensitive Single Molecule Array (SIMOA) technology to measure the levels of the inflammatory mediators Interleukin 6 (IL-6), Interleukin 17A (IL-17A), Tumour Necrosis Factor ␣ (TNF␣) and Transforming Growth Factor ␤ (TGF␤) in plasma from PD patients and age-and gender-matched healthy controls. We report that IL-17A correlates with non-motor symptoms (NMS) scores, while IL-6 positively correlates with motor scores. We found no correlations between cytokines and disease duration suggesting that IL-6 and IL-17A are associated with disease severity rather than disease duration in this cohort, furthermore IL-17A may be involved in the underlying pathophysiology of NMS in PD.

Effects of COVID‐19 on Parkinson's Disease Clinical Features: A Community‐Based Case‐Control Study

“…COVID-19 induced a significant worsening of motor performance, motor-related disability, and experiences of daily living. Worsening of levodopa-responsive motor symptoms and increased daily off time, caused either by the effects of acute systemic inflammatory response [6][7][8][9] or by changes in pharmacokinetics, was so pronounced in one third of cases to prompt neurologists to increase dopaminergic therapy. We explored the relative contribution of suboptimal absorption of oral therapy by adjusting motor end points for diarrhea, which was present in 50% of cases.…”

“…COVID-19 may worsen PD by a number of mechanisms, [2][3][4] including pharmacodynamics changes (eg, reciprocal interactions between the dopaminergic and renin-angiotensin systems in the substantia nigra and striatum 5 ) as well as systemic inflammatory responses. [6][7][8][9] Patients with PD are frailer than the general population because of disease-related factors and agerelated comorbidities. [2][3][4]10,11 A higher COVID-19 mortality rate has been described in advanced PD patients in association with older age and longer disease duration.…”

A Canadian perspective on severe acute respiratory syndrome coronavirus 2 infection and treatment: how prevalent underlying inflammatory disease contributes to pathogenesis

“…Furthermore, using neurotoxin-induced rodent models of PD, it has been demonstrated that adoptive transfer of T H 17 cells into the midbrain resulted in increased IL-17 production, activation of microglia and dopaminergic neuron death, supporting the role of T H 17 cells in PD pathogenesis (Liu et al 2019). A positive correlation between serum levels of IL-6 and IL-17 and severity of motor and non-motor symptoms were reported in a cohort of PD patients (Green et al 2019). It is noteworthy that the severity of COVID-19 disease has been shown to positively correlate with IL-17 levels and related T H 17 cytokines, such as IL-1β, IL-6 and TNF-α that are known to promote vascular permeability and leakage, which could allow trafficking of T H 17 across the blood-brain barrier (Pacha et al 2020).…”

Positive association of Parkinson’s disease with ankylosing spondylitis: a nationwide population-based study

“…Dysfunction of the immune system, such as autoimmune response, may involve in the pathogenesis of the disease. [9] Pro-inflammatory cytokines, specifically TNF-ɑ and IL-6, are significantly increased in the serum and cerebrospinal fluid of PD patients [10][11][12][13][14][15]. Furthermore, recent studies revealed that serum IL-6 and IL-17 positively correlate with severity of symptoms in PD [12,14].…”