Role of Interleukin 6 Inhibitors in the Management of Rheumatoid Arthritis

The role of interleukin (IL)-6 in health and disease has been under a lot of scrutiny in recent years, particularly during the recent COVID-19 pandemic. The inflammatory pathways in which IL-6 is involved are also partly responsible of the development and progression of rheumatoid arthritis (RA), opening interesting perspectives in terms of therapy. Anti-IL-6 drugs are being used with variable degrees of success in other diseases and are being tested in RA. Results have been encouraging, particularly when anti-IL-6 has been used with other drugs, such as metothrexate (MTX). In this review we discuss the main immunologic aspects that make anti-IL-6 a good candidate in RA, but despite the main therapeutic options available to target IL-6, no gold standard treatment has been established so far.

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Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: The role of acute-phase reactants

Arthritis & Rheumatism ◽

10.1002/art.27740 ◽

2010 ◽

Vol 63 (1) ◽

pp. 43-52 ◽

Cited By ~ 91

Author(s):

Josef S. Smolen ◽

Daniel Aletaha

Keyword(s):

Rheumatoid Arthritis ◽

Acute Phase ◽

Interleukin 6 ◽

Acute Phase Reactants ◽

Disease Remission ◽

Receptor Inhibition ◽

Interleukin 6 Receptor

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Primary pathologic role of interleukin-6 in rheumatoid arthritis

Italian Journal of Medicine ◽

10.4081/itjm.2008.4.40 ◽

2013 ◽

pp. 40-46

Author(s):

G.L. Bajocchi ◽

N. Pipitone ◽

P.L. Boiardi ◽

C. Salvarani

Keyword(s):

Rheumatoid Arthritis ◽

Interleukin 6 ◽

Cultured Cells ◽

Inflammatory Diseases ◽

Acute Phase Reactant ◽

Therapeutic Benefit ◽

Phase Iii ◽

Tnf Alpha ◽

Proinflammatory Activity

BACKGROUND Interleukin-6 (IL-6) is a polyfunctional cytokine that regulates a very large number of cellular activities. Its implication in acute-phase reactant production by hepatocytes is of particular interest, as is its involvement in chronic inflammatory diseases, mainly rheumatoid arthritis, Crohn’s disease, and Castleman’s disease. Transgenic mice lacking IL-6 expression were completely protected against collagen-induced arthritis, and Tumor Necrosis Factor (TNF-alpha) induces synovial cells to produce IL-6 and their proliferation. However, there is still some controversies regarding the unique proinflammatory activity of IL-6. Some studies have demonstrated that IL-6 and TNF-alpha may have an opposite effect in synovial cultured cells since IL-6 could represent a negative loop for TNF-alpha induced synovitis. However, phase III studies of rheumatoid arthritis patients treated with anti IL-6 receptor (tocilizumab) indicate an acceptable safety profile relative to the clinical benefit. AIM OF THE STUDY In this review, we summarized the rationale and the main evidence regarding the therapeutic benefit of blocking IL-6 activity in rheumatoid arthritis.

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The Effects of Gene Polymorphisms in Interleukin-4 and Interleukin-6 on the Susceptibility of Rheumatoid Arthritis in a Chinese Population

BioMed Research International ◽

10.1155/2014/265435 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Xiang Li ◽

Wei Chai ◽

Ming Ni ◽

Meng Xu ◽

Zijian Lian ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Healthy Volunteers ◽

Interleukin 6 ◽

Gene Polymorphisms ◽

Chinese Population ◽

Chinese Patients ◽

Interleukin 4 ◽

Promoter Polymorphisms ◽

Increased Risk

Background. Interleukin-4 (IL-4) and interleukin-6 (IL-6) have been reported to associate with pathogenesis of rheumatoid arthritis (RA); however, the role of IL-4 and IL-6 genetic polymorphisms in RA remains unknown.Method. A total of 752 unrelated Chinese patients with RA and 798 healthy Chinese volunteers with no family histories of any autoimmune diseases were recruited. The promoter IL-4-590 C/T and IL-6-174 G/C polymorphisms were genotyped.Result. The genotype distributions and allele frequencies of IL-4-590 C/T and IL-6-174 G/C polymorphisms in RA patients were significantly different from healthy volunteers. Statistically significant differences were observed in genotypes for IL-4-590 and IL-6-174. The frequencies of both the T allele on the IL-4-590 and the C on the IL-6-174 were significantly increased in RA patients.Conclusion. The IL-4-590 and IL-6-174 promoter polymorphisms may be associated with increased risk of RA and could be used as genetic marker for assessing the susceptibility and severity of RA in Chinese.

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