Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The Contribution of Tumor Necrosis Factor to Multiple Sclerosis Progression Independent of Relapses

Valentina Mazziotti
ORCID logo ,
Francesco Crescenzo
ORCID logo ,
Ermanna Turano
ORCID logo ,
Maddalena Guandalini
,
Maddalena Bertolazzo
,
Stefano Ziccardi
ORCID logo ,
Federica Virla
,
Valentina Camera
,
Damiano Marastoni
,
Agnese Tamanti
,
Massimiliano Calabrese
* ORCID logo
Version 1 : Received: 8 January 2024 / Approved: 10 January 2024 / Online: 10 January 2024 (09:54:47 CET)

How to cite: Mazziotti, V.; Crescenzo, F.; Turano, E.; Guandalini, M.; Bertolazzo, M.; Ziccardi, S.; Virla, F.; Camera, V.; Marastoni, D.; Tamanti, A.; Calabrese, M. The Contribution of Tumor Necrosis Factor to Multiple Sclerosis Progression Independent of Relapses. Preprints 2024, 2024010765. https://doi.org/10.20944/preprints202401.0765.v1 Mazziotti, V.; Crescenzo, F.; Turano, E.; Guandalini, M.; Bertolazzo, M.; Ziccardi, S.; Virla, F.; Camera, V.; Marastoni, D.; Tamanti, A.; Calabrese, M. The Contribution of Tumor Necrosis Factor to Multiple Sclerosis Progression Independent of Relapses. Preprints 2024, 2024010765. https://doi.org/10.20944/preprints202401.0765.v1

Abstract

Tumor necrosis factor (TNF) is a pleiotropic cytokine regulating many physiological and pathological immune-mediated processes. Although initially described as a tumor-cytotoxic agent, over time, it has also been recognized as an essential pro-inflammatory cytokine implicated in the pathogenesis of different autoimmune diseases, such as multiple sclerosis (MS). Several studies have shown an increase in TNF expression both in acute and chronic active MS brain lesions, as well as its involvement in maintaining a chronic inflammatory intrathecal process known as “compartmentalized inflammation”, which contributes to disease progression and disability accumulation in MS, even more than acute inflammatory activity. Indeed, high TNF levels were observed in the serum and cerebrospinal fluid of subjects with MS and correlated to disease severity, promoting axonal damage and, consequently, neurodegeneration. In this review we discuss the current knowledge of TNF and its receptors involvement in MS progression, focusing on disability progression independent of relapse activity (PIRA), meant as the disability accumulation evident in relapsing MS patients not related to acute inflammatory events.

Keywords

TNF biology; MS pathology; PIRA; MS lesions; chronic compartmentalized inflammation; neurodegeneration; biomarkers; disease progression. 1. Introduction

Subject

Biology and Life Sciences, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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