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OBJECTIVES: The degradation of tryptophan by indoleamine 2,3-dioxygenase yields a number of immunomodulatory metabolites, including 3-hydroxyanthranilic acid, 3-hydroxykynurenic acid and quinolinic acid. N-(3',4'-dimethoxycinnamonyl) anthranilic acid (3,4-DAA) is a synthetic anthranilic acid derivative that has been used therapeutically in Japan for many years as an anti-allergic drug and has recently been shown to be effective in a murine model of multiple sclerosis. METHODS: In the present study, we tested the efficacy of 3,4-DAA in collagen-induced arthritis, a mouse model of rheumatoid arthritis, and analysed its mechanism of action. RESULTS: Administration of 3,4-DAA after arthritis onset reduced clinical and histological severity of arthritis and reduced pain. It completely abrogated thermal and mechanical hyperalgesia. 3,4-DAA also suppressed Th1 cell activity in lymph node cell cultures and raised serum levels of IL-10. In vitro, 3,4-DAA suppressed IFNgamma production and proliferation of both T and B lymphocytes in a manner comparable with the endogenous tryptophan metabolite, 3-hydroxyanthranilic acid, suggesting similar mechanisms of action. CONCLUSION: It is concluded that 3,4-DAA has both anti-inflammatory and analgesic properties, and may therefore be useful in filling an unmet need, in the treatment of rheumatoid and other forms of arthritis, especially in the light of its analgesic properties.

Original publication

DOI

10.1093/rheumatology/kem160

Type

Journal article

Journal

Rheumatology (Oxford, England)

Publication Date

09/2007

Volume

46

Pages

1428 - 1432

Addresses

Kennedy Institute of Rheumatology, Imperial College London, London W6 8LH, UK.

Keywords

B-Lymphocytes, T-Lymphocytes, Animals, Mice, Inbred DBA, Mice, Arthritis, Experimental, Arthritis, Rheumatoid, Hyperalgesia, Disease Models, Animal, Anthranilic Acids, 3-Hydroxyanthranilic Acid, Analgesics, Non-Narcotic, Anti-Inflammatory Agents, Non-Steroidal, Drug Evaluation, Preclinical, Lymphocyte Activation, Dose-Response Relationship, Drug, Male