tranilast and Multiple-Sclerosis

Local catabolism of the amino acid tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. We show that IDO transcription was increased when myelin-specific T cells were stimulated with tolerogenic altered self-peptides. Catabolites of Trp suppressed proliferation of myelin-specific T cells and inhibited production of proinflammatory T helper-1 (T(H)1) cytokines. N-(3,4,-Dimethoxycinnamoyl) anthranilic acid (3,4-DAA), an orally active synthetic derivative of the Trp metabolite anthranilic acid, reversed paralysis in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis (MS). Trp catabolites and their derivatives offer a new strategy for treating T(H)1-mediated autoimmune diseases such as MS.

Topics: Adoptive Transfer; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigen-Presenting Cells; Brain; Cell Line; Cytokines; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Histocompatibility Antigens Class II; Immune Tolerance; Immunosuppressive Agents; Indoleamine-Pyrrole 2,3,-Dioxygenase; Interferon-gamma; Lymphocyte Activation; Mice; Mice, Transgenic; Microglia; Multiple Sclerosis; Myelin Proteins; ortho-Aminobenzoates; Signal Transduction; Spinal Cord; T-Lymphocytes; Th1 Cells; Th2 Cells; Tryptophan