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Review
. 2020 Sep;7(3):473-516.
doi: 10.1007/s40744-020-00219-2. Epub 2020 Jul 30.

Understanding the Role of Interleukin-6 (IL-6) in the Joint and Beyond: A Comprehensive Review of IL-6 Inhibition for the Management of Rheumatoid Arthritis

Ennio G Favalli  1
Affiliations
Review

Understanding the Role of Interleukin-6 (IL-6) in the Joint and Beyond: A Comprehensive Review of IL-6 Inhibition for the Management of Rheumatoid Arthritis

Ennio G Favalli. Rheumatol Ther. 2020 Sep.

Abstract

Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune disorder involving inflammation and progressive destruction of the joints, affecting up to 1% of the population. The majority of patients with RA have one or more comorbid conditions, the most common being cardiovascular disease, osteoporosis, and depression, the presence of which are associated with poorer clinical outcomes and lower health-related quality of life. RA pathogenesis is driven by a complex network of proinflammatory cells and cytokines, and of these, interleukin-6 (IL-6) plays a key role in the chronic inflammation associated with RA. Through cell signaling that can be initiated by both membrane-bound and soluble forms of its receptor, IL-6 acts both locally to promote joint inflammation and destruction, and in the circulation to mediate extra-articular manifestations of RA, including pain, fatigue, morning stiffness, anemia, and weight loss. This narrative review describes the role of IL-6 in the pathogenesis of RA, its comorbidities, and extra-articular systemic manifestations, and examines the effects of the IL-6 receptor inhibitors sarilumab and tocilizumab on clinical endpoints of RA, patient-reported outcomes, and common comorbidities and extra-articular manifestations.

Keywords: Antirheumatic agents; C-reactive protein; Comorbidity; Inflammation; Interleukin-6; Rheumatoid arthritis.

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Conflict of interest statement

Ennio G. Favalli has received consulting fees and/or speaking engagements from AbbVie, Bristol-Myers Squibb, Lilly, Merck Sharp & Dohme, Pfizer, Roche, Sanofi Genzyme, and Union Chimique Belge.

Figures

Fig. 1
Fig. 1
IL-6 as a pleiotropic cytokine. CNS central nervous system, CRP C-reactive protein, HPA hypothalamic–pituitary–adrenal, IL-6 interleukin-6, IL-8 interleukin-8, RA rheumatoid arthritis, RANKL Receptor Activator of Nuclear Factor-κB Ligand. Body image, Mikael Häggström https://commons.wikimedia.org/w/index.php?curid=15298838
Fig. 2
Fig. 2
The classical (or cis-) and trans-signaling pathways of IL-6. gp130 glycoprotein 130, IL-6 interleukin-6, IL-6Rα interleukin-6 receptor alpha, JAK Janus kinase, MAPK mitogen-activated protein kinase, P phosphate, SOCS3 suppressor of cytokine signaling 3, STAT3 signal transducer and activator of transcription 3, Y tyrosine
See this image and copyright information in PMC

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