Urinary tryptophan metabolites in rheumatoid arthritis and some other diseases.

Previous studies from this laboratory have shown that a majority of patients with rheumatoid arthritis excrete abnormally high amounts of 3-hydroxyanthranilic acid and kynurenine (Bett, 1962a, b). A more striking finding was the rise in kynurenine output after tryptophan loading in rheumatoid arthritis. Administration of large doses of pyridoxine over a short period caused a temporary fall in kynurenine output which increased again when the test was repeated after pyridoxine had been withdrawn for a week. Urinary tryptophan metabolites have been studied in a variety of diseases including rheumatoid arthritis and it is known that abnormalities in the metabolism of this amino acid are not specific to this particular disease. Flinn, Price, Yess, and Brown (1964) refer to studies in which increased amounts of several metabolites were found in the urine of patients with bladder cancer, scleroderma, acrosclerosis, porphyria and lupus erythematosus, and in pregnant women. No abnormalities were found in patients with psoriasis, atopic dermatitis, hyperthyroidism, muscular dystrophy, Friedrich's ataxia, or diabetes mellitus. These authors also measured kynurenic acid, xanthurenic acid, indoxyl sulphate, anthranilic acid glucuronide, o-aminohippuric acid, N-a-acetyl kynurenine, kynurenine, 3-hydroxykynurenine, and pyridone in the urines of fifteen female and five male patients with rheumatoid arthritis. After tryptophan loading they found significantly raised levels of one or more of the metabolites measured in twelve of the fifteen female patients and in four of the five male patients. Kynurenine and 3-hydroxykynurenine were most frequently elevated. Pyridoxine restored metabolism to normal in eleven female patients studied, although it had been shown previously that excretion of 4-pyridoxic acid was normal in these patients. Spiera (1963) and Spiera and Plotz (1964) found that a significant number of patients with rheumatoid arthritis excreted increased quantities of kynurenine, 3-hydroxyanthranilic acid, and xanthurenic acid as compared with patients suffering from other connective tissue diseases and with a group of patients with other diseases. Pinals (1964) has also measured a series of tryptophan metabolites in patients with rheumatoid arthritis, other connective tissue disease, and other diseases, and concluded that kynurenine and 3-hydroxykynurenine were excreted in increased amounts non-specifically in rheumatoid arthritis. Excretion did not correlate well with indices of clinical activity of disease. In the present study kynurenine, 3-hydroxykynurenine, kynurenic acid, xanthurenic acid, anthranilic acid, and N-methylnicotinamide (pyridone) have been measured before and after 3 g. L-tryptophan given by mouth in patients suffering from rheumatoid arthritis, patients with other diseases affecting connective tissue, and patients with a variety of other diseases. For technical reasons 3-hydroxyanthranilic acid was not measured concurrently.