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.