Combination treatment of docosahexaenoic acid (DHA) and all-trans-retinoic acid (ATRA) inhibit IL-17 and RORγt gene expression in PBMCs of patients with relapsing-remitting multiple sclerosis

Abstract

Objectives: Multiple sclerosis (MS) is a demyelinating disorder with a complex autoimmune pathophysiology. Its initiation and progression correlate with IL-17 and the related transcription factor, RORγt. All-trans retinoic acid (ATRA) is a bioactive derivative of vitamin A, and docosahexaenoic acid (DHA) is an active metabolite of omega-3 fatty acid; both have immunomodulatory effects in many immune disorders. This study investigated the effects of DHA and ATRA individually and in combination on IL-17 and RORγt gene expression in peripheral blood mononuclear cells (PBMCs) of relapsing–remitting MS (RRMS) patients who were receiving interferon beta (IFN-β).

Methods: The PBMCs of 15 RRMS patients were treated in vitro with 1 μM of ATRA and 15 μM of DHA as single and combination treatments for assessing probable additive or synergistic effects.

Results: The results showed that single treatment of ATRA (p = 0.05) could significantly decrease the expression of IL-17 gene and single treatment of ATRA (p = 0.04) and single treatment of DHA (p = 0.05) induced significant inhibition on the expression of RORγt gene. The suppressive effect of combined treatment with ATRA and DHA on IL-17 (p = 0.02) and RORγt (p = 0.01) was also found significant showing that the combined treatments can have additive effects.

Discussion: These results indicate that both DHA and ATRA might help control disease progression in IFN-β treated RRMS patients with the strongest effects produced by a combination of the two compounds.

Keywords:

• Multiple sclerosis
• PBMCs
• interleukine-17
• RORγt
• docosahexaenoic acid
• all-trans retinoic acid

Acknowledgments

The authors of this article appreciate all MS patients who voluntarily participated in this research project. This study was carried out at the School of Nutritional Sciences and Dietetics and School of Public Health, International Campus, supported by the International Campus, TUMS, Tehran, Iran.