Assessment of Interleukin-17A, Interleukin-10 and Transforming Growth Factor-Beta1 Serum Titers in Relapsing Remitting Multiple Sclerosis Patients Treated with Avonex, Possible Biomarkers for Treatment Response

Abstract

Introduction: Individual response to interferon beta (IFN-β) 1a treatment is heterogeneous in multiple sclerosis (MS). Our objective was to find a connection between serum levels of interleukin (IL)-10, IL-17 and transforming growth factor beta (TGF-β)1 in MS patients treated with IFN-β in order to identify the nonresponders (NR).

Material and methods: We included in the study 32 healthy subjects and 32 MS patients: 10 naive, 10 early treated and 12 late treated with INF-β1a. Serum determination of cytokines and brain MRI were performed at the beginning of the study, after 6 and 12 months. Rio score was calculated at the end of the study.

Results: MS patients had initially a significant higher level of IL-17 and a lower level of TGF-β1 compared to healthy subjects. IL-17 level in early treated patients was significantly lower compared to the naive and late treated groups. INF-β1a treatment significantly increased IL-10 and decreased IL-17 levels. Initial low levels of IL-10 were associated with an increase in physical disability. IL-17 levels positively correlated with the number of relapses and MRI activity. Nine patients were NR to Avonex. Patients with a Rio score of 3 had higher initial levels of IL-17 and those with a Rio score of 0 had higher initial levels of IL-10 and TGF-β1.

Conclusion: IFN-β1a decreased IL-17 and increased IL-10 seric levels; IL-17 significantly correlated with MS activity; TGF-β1 activity is titer-dependent, increased levels were associated with IL-17 inhibition; NR patients to IFN-β1a will have initial high IL-17 and low IL-10 and TGF-β seric levels.

Keywords: Avonex; Interferon beta; disease modifying therapies; interleukin-10; interleukin-17A; multiple sclerosis; transforming growth factor-beta1..