Tocilizumab improves the proatherothrombotic profile of rheumatoid arthritis patients modulating endothelial dysfunction, NETosis, and inflammation

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Tocilizumab improves the proatherothrombotic profile of rheumatoid arthritis patients modulating endothelial dysfunction, NETosis, and inflammation

Tocilizumab (TCZ) is an efficacious drug for the treatment of rheumatoid arthritis (RA). However, adverse effects associated with TCZ therapy on endothelial dysfunction, monocyte activity, NETosis, and oxidative stress, the principal effectors of atherosclerosis and cardiovascular disease, have not been analyzed yet.

To serve this purpose, a total of 20 RA patients received 162 mg per week subcutaneous (SC) TCZ for 6 months. Laser doppler was used to measure the endothelial function through postocclusive hyperemia. The oxidative stress markers in monocytes and neutrophils were estimated by flow cytometry. NETosis was measured via SYTOX staining of DNA fibers and the expression of myeloperoxidase and neutrophil elastase. Flow cytometry was used to find out the percentage of low-density granulocytes. In the monocytes, the gene expression  and phosphorylation of intracellular pathways was estimated.

It was revealed that TCZ enhanced the endothelial function and decreased the oxidative stress in RA leukocytes. The percentage of low-density granulocytes and NETosis generation lessened. Through the modulation of specific intracellular pathways, the proinflammatory and prothrombotic status of RA monocytes was also reversed. All these outcomes were reviewed after in vitro treatment with TCZ of monocytes and neutrophils purified from RA patients and cocultured with endothelial cells.

It was found that TCZ might reduce the proatherothrombotic profile in RA patients via the restoration of the endothelial function, oxidative stress reduction, inhibition of monocytes' prothrombotic and inflammatory profile, and abridged NETosis generation.

Source:

The Journal of Laboratory and Clinical Medicine

Link to the source:

http://www.translationalres.com/article/S1931-5244(16)30423-6/abstract

Original title of article:

Tocilizumab improves the proatherothrombotic profile of rheumatoid arthritis patients modulating endothelial dysfunction, NETosis, and inflammation

Authors:

P. Ruiz-Limon et al.

The Journal of Laboratory and Clinical Medicine
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