Τίτλος:
Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
We investigated the effects of tocilizumab on endothelial glycocalyx, a determinant of vascular permeability, and myocardial function in rheumatoid arthritis (RA). Eighty RA patients were randomized to tocilizumab (n = 40) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids (GC) (n = 40) for 3 months. Forty healthy subjects with similar age and sex served as controls. We measured: (a)perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), (b)pulse wave velocity (PWV), (c)global LV longitudinal strain (GLS), (d)global work index (GWI) using speckle tracking echocardiography and e)C-reactive protein (CRP), malondialdehyde (MDA) and protein carbonyls (PCs) as oxidative stress markers at baseline and post-treatment. Compared to controls, RA patients had impaired glycocalyx and myocardial deformation markers (P < 0.05). Compared with baseline, tocilizumab reduced PBR(2.14 ± 0.2 versus 1.97 ± 0.2 μm; P < 0.05) while no significant differences were observed post-csDMARDs + GC(P > 0.05). Compared with csDMARDs + GC, tocilizumab achieved a greater increase of GLS, GWI and reduction of MDA, PCs and CRP(P < 0.05). The percent improvement of glycocalyx thickness (PBR) was associated with the percent decrease of PWV, MDA, PCs and the percent improvement of GLS and GWI(P < 0.05). Tocilizumab improves endothelial function leading to a greater increase of effective myocardial work than csDMARDs + GC through a profound reduction of inflammatory burden and oxidative stress. This mechanism may explain the effects of tocilizumab on COVID-19. Clinical trial registration: url: https://www.clinicaltrials.gov. Unique identifier: NCT03288584. © 2020
Συγγραφείς:
Ikonomidis, I.
Pavlidis, G.
Katsimbri, P.
Lambadiari, V.
Parissis, J.
Andreadou, I.
Tsoumani, M.
Boumpas, D.
Kouretas, D.
Iliodromitis, E.
Περιοδικό:
Food and Chemical Toxicology
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
antidiabetic agent; beta adrenergic receptor blocking agent; C reactive protein; calcium channel blocking agent; carbonyl derivative; dipeptidyl carboxypeptidase inhibitor; disease modifying antirheumatic drug; diuretic agent; glucocorticoid; hydroxymethylglutaryl coenzyme A reductase inhibitor; leflunomide; malonaldehyde; methotrexate; prednisolone; tocilizumab; IL6 protein, human; interleukin 6; monoclonal antibody; tocilizumab, adult; Article; blood vessel parameters; blood vessel permeability; controlled study; coronavirus disease 2019; diabetes mellitus; drug dose increase; endothelium cell; female; global left ventricular longitudinal strain; global work index; glycocalyx; heart function; human; major clinical study; male; microvasculature; oxidative stress; perfused boundary region; pulse wave; randomized controlled trial; rheumatoid arthritis; speckle tracking echocardiography; sublingual arterial microvessel; thickness; treatment duration; aged; Betacoronavirus; capillary permeability; Coronavirus infection; drug effect; endothelium; glycocalyx; heart; inflammation; middle aged; oxidative stress; pandemic; rheumatoid arthritis; virus pneumonia, Aged; Antibodies, Monoclonal, Humanized; Arthritis, Rheumatoid; Betacoronavirus; Capillary Permeability; Coronavirus Infections; Endothelium; Female; Glycocalyx; Heart; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Oxidative Stress; Pandemics; Pneumonia, Viral; Pulse Wave Analysis
DOI:
10.1016/j.fct.2020.111694
