The anti-allergic drug, N-(3',4'-dimethoxycinnamonyl) anthranilic acid, exhibits potent anti-inflammatory and analgesic properties in arthritis.
OBJECTIVE
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.


CONCLUSIONS
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.
Inglis
J J
JJ
Kennedy Institute of Rheumatology, Imperial College London, London W6 8LH, UK.
Criado
G
G
Andrews
M
M
Feldmann
M
M
Williams
R O
RO
Selley
M L
ML
D015095:3-Hydroxyanthranilic Acid / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006930:Hyperalgesia / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D062367:ortho-Aminobenzoates / Q000627:therapeutic use*
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D062367:ortho-Aminobenzoates; D015095:3-Hydroxyanthranilic Acid; C012293:tranilast