Correlation of interleukin 6 and transforming growth factor β1 with peripheral blood regulatory T cells in rheumatoid arthritis patients: a potential biomarker

Majid Khoshmirsafa; Farhad Seif; Nader Bagheri; Pezhman Beshkar; Mohammad Mousavi; Hedayatollah Shirzad

doi:10.5114/ceji.2018.80047

Correlation of interleukin 6 and transforming growth factor β1 with peripheral blood regulatory T cells in rheumatoid arthritis patients: a potential biomarker

Cent Eur J Immunol. 2018;43(3):281-288. doi: 10.5114/ceji.2018.80047. Epub 2018 Oct 30.

Authors

Majid Khoshmirsafa^{1

2}, Farhad Seif^{1

2}, Nader Bagheri¹, Pezhman Beshkar¹, Mohammad Mousavi³, Hedayatollah Shirzad^{1

4

5}

Affiliations

¹ Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
² Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran.
³ Department of Internal Medicine, Imam Ali Hospital, Shahrekord University of Medical Sciences, Shahrekord, Iran.
⁴ Department of Microbiology and Immunology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
⁵ Medicinal Plant Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Abstract

Introduction: Proinflammatory cytokines and regulatory T cells (Tregs) are considered as important factors involved in autoimmunity development especially in rheumatoid arthritis (RA).

Aim of the study: To investigate the frequency of peripheral blood Tregs and related cytokines in RA patients and to determine the possible correlation between Treg percentage and interleukin 6 (IL-6) and transforming growth factor β1 (TGF-β1) as indicators in assessment of Treg function and mechanisms preceding autoimmunity in RA.

Material and methods: Thirty-seven Iranian RA patients with a moderate (3.2-5.1) disease activity score (DAS) and the same number of healthy age- and sex-matched individuals were enrolled. Frequency of peripheral blood Tregs (CD4⁺FoxP3⁺CD25^high) was determined by flow cytometry. Serum levels of IL-6 and TGF-β1 and their expression levels in peripheral blood mononuclear cells (PBMCs) were evaluated by ELISA and Q-PCR, respectively.

Results: Rheumatoid arthritis patients showed significantly lower peripheral blood Treg frequencies compared to healthy individuals. Additionally, Treg (%) showed a significant inverse correlation between serum concentrations of IL-6 and mRNA expression of PBMCs, whereas there was no significant correlation between Treg (%) and TGF-β1 levels.

Conclusions: The current study revealed that Treg numbers were reduced in peripheral blood of RA patients. This reduction inversely correlated with IL-6 levels, which may lead to persistent autoimmune and inflammatory conditions in RA patients.

Keywords: IL-6; TGF-β1; regulatory T cells; rheumatoid arthritis.