Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19. (November 2020)

• Record Type: Journal Article
• Authors: Ikonomidis, Ignatios; Pavlidis, George; Katsimbri, Pelagia; Lambadiari, Vaia; Parissis, John; Andreadou, Ioanna; Tsoumani, Maria; Boumpas, Dimitrios; Kouretas, Dimitrios; Iliodromitis, Efstathios
• Is Part Of: Food and chemical toxicology. Volume 145(2020)
• Publication Date: 2020-11
• Subjects: Rheumatoid arthritis -- Interleukin 6 -- Tocilizumab -- Endothelial glycocalyx -- Myocardial deformation -- COVID-19; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2020.111694
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: 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. Highlights: Tocilizumab improves endothelial glycocalyx and increases effective myocardial work. IL-6 inhibition significantly reduces the inflammatory burden and oxidative stress. Tocilizumab may have favorable effects on diseases with excess IL-6 release.