Plasma levels of IL-37 and correlation with TNF-α, IL-17A, and disease activity during DMARD treatment of rheumatoid arthritis.

Ping-Wei Zhao,Wei-Guang Jiang,Li Wang,Zhen-Yu Jiang,Yu-Xing Shan,Yan-Fang Jiang,Josep Bassaganya-Riera

doi:10.1371/journal.pone.0095346

Abstract

The aim of this study was to assess the change of IL-37 concentrations in rheumatoid arthritis (RA) patients under Disease-modifying anti-rheumatic drug (DMARD) therapy, and to establish a correlation between Interleukin-37 and pro-inflammatory cytokines in plasma and disease activity. The plasma level of IL-37 was determined using ELISA in 50 newly diagnosed RA patients and 30 healthy controls (HC). Plasma levels of IL-17A, IL-6 and TNF-α were measured using flow a cytometric bead array assay. We found that the concentrations of IL-37, as well as IL-17A, IL-6 and TNF-α, were higher in plasma of RA patients compared to HCs. Compared to patients who did not respond to DMARD treatment, treatment of patients responsive to DMARDs resulted in down-regulation of IL-17A, IL-6 and TNF-α expression. The plasma level of the anti-inflammatory cytokine IL-37 was also decreased in drug responders after DMARD treatment. The plasma level of IL-37 in RA patients was positively correlated with pro-inflammatory cytokines (IL-17A, TNF-α) and disease activity (CRP, DAS28) in RA patients. IL-37 expression in RA and during DMARD treatment appears to be controlled by the level of pro-inflammatory cytokines. This results in a strong correlation between plasma levels of IL-37 and disease activity in RA patients.

Highlights

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with autoimmune etiology characterized by joint inflammation, T cell infiltration of the synovium, synovial hyperplasia, neoangiogenesis, involvement of many catabolic cytokines, and progressive destruction of articular cartilage and bone [1]
Based on the effect of Diseasemodifying anti-rheumatic drug (DMARD) treatment on the disease activity score 28 (DAS28) score, the 50 RA patients were divided into two groups: 34 patients were determined as being responsive to DMARD treatment, while the other 16 patients were determined to be unresponsive to DMARD treatment
There are currently two hypotheses: either IL-37 is secreted into the extracellular space to inhibit the actions of pro-inflammatory cytokines or their receptors [23], or IL-37 translocates to the nucleus where it interacts with Smad3 to interrupt transcription of pro-inflammatory cytokine genes [10,12,13]

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with autoimmune etiology characterized by joint inflammation, T cell infiltration of the synovium, synovial hyperplasia, neoangiogenesis, involvement of many catabolic cytokines, and progressive destruction of articular cartilage and bone [1]. TNF-a is a pivotal pro-inflammatory cytokine in the pathogenesis of RA that is known to induce adhesion molecule and proteinase gene expression, and play a major role in the progression of joint destruction and proliferation of synoviocytes [3]. IL-17A is one of the most important mediators involved in T cellmediated synovial inflammation and contributes to bone destruction through increase of migration, chemokine gene expression, and invasiveness of synoviocytes in RA [7,8]. Therapies targeting these cytokines or their receptors are recognized as effective treatments for patients with RA [9]

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