tretinoin and Multiple-Sclerosis--Relapsing-Remitting

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).. 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.. 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.. 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.

Topics: Adult; Disability Evaluation; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Drug Combinations; Female; Gene Expression; Humans; Interferon-beta; Interleukin-17; Leukocytes, Mononuclear; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Nuclear Receptor Subfamily 1, Group F, Member 3; RNA, Messenger; Tretinoin; Young Adult

We have explored the beneficial effects of retinoic acid (RA) on B cells from multiple sclerosis (MS) patients. When co-stimulated via the toll-like receptors (TLRs) TLR9 and RP105, MS B cells secreted less of the anti-inflammatory cytokine interleukin 10 (IL-10) compared to B cells from healthy controls. Importantly, RA enhanced the secretion of IL-10 by MS-derived B cells without affecting the levels of the pro-inflammatory cytokine TNF-α. RA revealed the same ability to induce IL-10 as did interferon-β-1b (IFN-β-1b), and B-cells from patients treated with glatiramer acetate or IFN-β-1b still displayed the beneficial effects of RA on the IL-10/TNF-α ratio.

Topics: Adult; Aged; Antigens, CD; Antigens, CD19; B-Lymphocytes; Cell Proliferation; Cells, Cultured; Female; Glatiramer Acetate; Humans; Immunosuppressive Agents; Interleukin-10; Keratolytic Agents; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Peptides; Toll-Like Receptor 9; Tretinoin; Tumor Necrosis Factor-alpha