Effect of Colchicine on Th1 and Th17 Cytokines, Cytokine Receptors, and Chemokine Gene Expression Profiles in Behçet's Disease

Eda Balkan,Nilnur Eyerci,Ibrahim Pirim,Sadullah Keles,Handan Bilen,Necmettin Akdeniz

doi:10.31586/dermatology.0402.01

Abstract

Objective: Colchicine has been used in recent years as an effective drug for controlling attacks in Behcet’s disease. In the present study, we investigated expression levels of IL1R, IL2R, IL12RB, IL23R, IL17, CXCR3, CXCR10 and IL8 genes in patients with active and inactive Behcet’s disease. We also evaluated how colchicine use in patients with active and inactive disease affected these genes and evaluated their role in the etiopathogenesis of the disease. Methods: Thirty-five patients who were diagnosed with Behcet’s disease according to the International Working Group criteria (28 with active disease, 7 inactive) and were taking colchicine were enrolled in the study. Twenty healthy subjects were included as a control group. Expression levels of the IL1R, IL2R, IL12RB, IL23R, IL17, CXCR3 ,CXCR10 and IL8, genes were evaluated. Results: Expression levels of CXCR3 and IL23R were significantly lower in patients with active Behcet's disease when compared with the inactive disease and control groups. However, the differences in CXCR3 and IL23R expression between the inactive Behcet’s patient group and the control group were nonsignificant. Expression levels of the other genes did not differ statistically between the active Behcet’s patients, inactive Behcet’s patients, and control subjects. Conclusion: While the expression levels of the CXCR3 and IL23R genes in active Behcet’s patients were statistically lower than controls, there was no statistical difference between active and inactive Behcet’s patients or controls in terms of IL1R, IL2R, IL17, IL12RB, CXCR10 and IL8, gene expression levels. This study may form the basis for further studies to determine the molecular mechanism of colchicine in the treatment of Behcet's disease.

Highlights

There are two groups of genes implicated in Behçet’s disease (BD) pathogenesis: those located within the major histocompatibility complex (MHC) locus, and those not in the MHC locus
The mRNA expression levels of IL23R and CXCR3 were significantly lower in the BD patients compared to controls (p
Immunodeficiencies triggered by genetic predisposition and certain environmental factors seem to play a role in the etiopathogenesis of BD

Summary

Introduction

Behçet’s disease (BD) is a chronic systemic inflammatory condition characterized by recurrent mucocutaneous findings and manifests with ocular, articular, vascular, neurological, pulmonary, and gastrointestinal multisystem involvement. IL-17 promotes the release of cytokines such as TNF, IL-1, IL-6, and IL-8 from monocytes, epithelial and endothelial cells, which causes neutrophil migration and activation and results in neutrophil-mediated inflammatory response. As the IL-17 pathway may play an important role in the communication between lymphocytes and neutrophils in BD patients, cytokines associated with this pathway may be important targets for treatment. Upregulation of IL-12 receptors has been shown to promote IFN-γ expression in Th0 cells and skew the Th1/Th2 balance towards Th1 dominance. The CXCR3 chemokine receptor is expressed on active Th1 cells, and studies have provided evidence that CXCR3 is the primary inflammatory chemokine receptor involved in BD. Recent studies have determined that serum CXCL10 level is associated with disease activity in BD. In the present study we investigated how colchicine affects gene expression by conducting expression profile analysis of IL1R, IL2R, IL12R, IL23R, IL17, CXCR3, CXCR10 and IL8, mRNA from peripheral blood samples of patients with active BD (exhibiting at least one sign of BD) and patients with inactive BD

Material Collection

Gene Expression Analysis

Results

Discussion