Soluble interleukin-1 receptor type 2 plasma levels in Parkinson's disease: relationship with cardiac autonomic profile before and after peripheral mechanical somatosensory stimulation

Dana Shiffer; Antonio Roberto Zamunér; Maura Minonzio; Mara Bulgheroni; Alberto Porta; Roberto Leone; Barbara Bottazzi; Cecilia Garlanda; Francesco Colotta; Franca Barbic; Alberto Mantovani; Raffaello Furlan

doi:10.3389/fphys.2023.1168652

Soluble interleukin-1 receptor type 2 plasma levels in Parkinson's disease: relationship with cardiac autonomic profile before and after peripheral mechanical somatosensory stimulation

Front Physiol. 2023 Aug 16:14:1168652. doi: 10.3389/fphys.2023.1168652. eCollection 2023.

Authors

Dana Shiffer^{1

2}, Antonio Roberto Zamunér³, Maura Minonzio², Mara Bulgheroni⁴, Alberto Porta^{5

6}, Roberto Leone⁷, Barbara Bottazzi⁷, Cecilia Garlanda^{1

7}, Francesco Colotta⁷, Franca Barbic^{1

2}, Alberto Mantovani^{1

7

8}, Raffaello Furlan^{1

2}

Affiliations

¹ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
² Internal Medicine, IRCCS Humanitas Research Hospital, Rozzano, Italy.
³ Departamento de Kinesiología, Universidad Católica Del Maule, Talca, Chile.
⁴ Department of Medicine, ASST Fatebenefratelli Sacco, Milan, Italy.
⁵ Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
⁶ Department of Cardiothoracic, Vascular Anesthesia and Intensive Care, IRCCS Policlinico di San Donato, San Donato Milanese, Italy.
⁷ IRCCS Humanitas Research Hospital, Milan, Italy.
⁸ The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.

Abstract

Introduction: Systemic inflammation promotes neurodegeneration in Parkinson's disease (PD). Interleukin-1 receptor type 2 (sIL-1R2) plasma levels increase during inflammation. Data on sIL-1R2 in PD patients and its relationship with PD cardiac autonomic profile are limited, given the possible anti-inflammatory effect of vagal activation. Previously, automated mechanical peripheral somatosensory stimulation (AMPSS) enhanced cardiac vagal modulation. Objectives were to 1) evaluate sIL-1R2 plasma concentrations in PD patients and healthy controls and 2) investigate the correlations between sIL-1R2 and cardiac autonomic indices obtained by spectrum analysis of heart rate variability before and after AMPSS. Methods: sIL-1R2 plasma levels were assessed in 48 PD patients and 50 healthy controls. Electrocardiogram and beat-by-beat arterial pressure were recorded at baseline and after 5 AMPSS sessions in 16 PD patients. Results: PD patients had higher sIL-1R2 levels than controls. In the PD subgroup, an inverse correlation between sIL-1R2 and HFnu was found. There was a negative correlation between changes induced by AMPSS on HFnu and sIL-1R2. Discussion: Higher sIL-1R2 levels in PD patients reflect the inflammatory dysregulation associated with the disease. In PD patients, higher sIL-1R2 was associated with reduced cardiovagal tone. Increased cardiovagal modulation following AMPSS was associated with lower sIL-1R2 levels in Parkinson's disease patients, suggesting inflammatory state improvement.

Keywords: Parkinson’s disease; cardiovascular autonomic control; heart rate variability; mechanical somatosensory stimulation; soluble interleukin-1 receptor type 2 (sIL-1R2).

Grants and funding

The current study was partially supported by a grant from Fondazione Humanitas per la Ricerca, by the Italian Ministry of Health (Grant #RF-2013-02355242) and by a liberal donation from Gondola Medical Technologies SA, Epalinges, Switzerland. The setting up and validation of the ELISA assays were conducted in the context of the INNOVA Platform supported by EU and Ministero della Salute (PNRR project PNC-E3-2022-23683266 PNC-HLS-DA).