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Selected cytokine pathways in rheumatoid arthritis

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Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. Cytokines play a key role in its pathogenesis. They contribute to the induction and maintenance of inflammation and thus provide therapeutic targets. Many cytokines are involved in RA, and this review focuses on a few critical ones: tumor necrosis factor (TNF), interleukin (IL)-6, IL-1, IL-17, and GM-CSF. TNF and IL-6 are both well-established targets in RA treatment, and new biologic agents are reaching the market. IL-1 represents a more complex cytokine as results in humans do not reach those in animal models. IL-17 and GM-CSF are cytokines representing new targets either as early treatment or in non-responders to other biologics. The interaction between cytokines and their signaling pathways are the basis for the development of new strategies with small molecules or bispecific antibodies. Clearly, the targeting of cytokines has been a major progress in RA treatment, but many issues remain open. Although remission can be better achieved, reactivation of the disease too often occurs upon treatment discontinuation. Better understanding and targeting of chronicity remains a goal to achieve in the future.

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Abbreviations

RA:

Rheumatoid arthritis

TNF(R):

Tumor necrosis factor (receptor)

IL:

Interleukin

TRADD:

TNFR1-associated death domain protein

NFκB:

Nuclear factor κB

MAPKs:

Mitogen-activated protein kinases

MLKL:

Mixed lineage kinase domain-like protein

TRAF:

TNFR-associated factor

PKB:

protein kinase B

TB:

Mycobacterium tuberculosis

CIA:

Collagen-induced arthritis

AIA:

Antigen-induced arthritis

FDA:

Food and Drug Administration

TCZ:

Tocilizumab

JAK:

Janus family tyrosine kinase

STAT:

Signal transducer and activator of transcription

SOCS:

Suppressor of cytokine signals

MyD88:

Myeloid differentiation primary response gene 88

IRAK:

IL-1 receptor-associated kinase

AP-1:

Activator protein 1

PI3K:

Phosphoinositide-3 kinase

CAPS:

Cryopyrin-associated periodic syndromes

MS:

Multiple sclerosis

DMARD:

Disease-modifying antirheumatic drugs

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  1. Immunogenomics and Inflammation Research Unit EA 4130, Department of Immunology and Rheumatology, University of Lyon, 69437, Lyon, Cedex 03, France

    Mélissa Noack & Pierre Miossec

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  1. Mélissa Noack
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This article is a contribution to the special issue on Immunopathology of Rheumatoid Arthritis - Guest Editors: Cem Gabay and Paul Hasler

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Noack, M., Miossec, P. Selected cytokine pathways in rheumatoid arthritis. Semin Immunopathol 39, 365–383 (2017). https://doi.org/10.1007/s00281-017-0619-z

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