Open AccessTryptophan metabolism via the kynurenine pathway in patients with the eosinophilia–Myalgia syndrome
Author(s) -
Silver Richard M.,
McKinley Kevin,
Smith Edwin A.,
Quearry Bonnie,
Harati Yadollah,
Sternberg Esther M.,
Heyes Melvyn P.
Publication year - 1992
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780350916
Subject(s) - quinolinic acid , kynurenine , asymptomatic , kynurenine pathway , medicine , endocrinology , indoleamine 2,3 dioxygenase , myalgia , corticosteroid , eosinophilia , ingestion , tryptophan , biology , biochemistry , amino acid
Objective. To investigate the metabolism of L‐tryptophan (LT) via the kynurenine pathway in patients with the eosinophilia–myalgia syndrome (EMS). Methods. Measurement of LT, L‐kynurenine, and quinolinic acid in plasma and cerebrospinal fluid (CSF) from subjects with EMS, from asymptomatic users of LT, and from normal subjects. Results. Plasma LT concentrations were lower in untreated EMS patients (n = 5) than in corticosteroid‐treated EMS patients (n = 5; P < 0.05) and in asymptomatic users of LT (n = 5; P < 0.05). Untreated EMS patients, who had discontinued LT weeks to months prior to study, had significantly higher plasma levels of L‐kynurenine and quinolinic acid than did corticosteroid‐treated EMS patients ( P < 0.05), normal subjects ( P < 0.02), and asymptomatic users of LT ( P < 0.05). EMS patients also had significantly elevated levels of L‐kynurenine ( P < 0.05) and quinolinic acid ( P < 0.001) in CSF compared with normal subjects. After a 1‐gm oral dose of LT, untreated EMS patients (n = 4) showed lower peak levels of LT and accentuated synthesis of L‐kynurenine and quinolinic acid, compared with these values in corticosteroid‐treated EMS patients (n = 2), who responded like normal subjects (n = 5). Conclusion. These data demonstrate that during the active phase of EMS, LT metabolism via the kynurenine pathway was accentuated, probably secondary to induction of the enzyme indoleamine‐2,3‐dioxygenase. Ingestion of large amounts of LT (median daily dose 1.5 gm) resulted in high concentrations of kynurenine‐pathway metabolites in blood and extrahepatic tissues, which was accentuated in EMS patients and which may have played a significant role in the pathogenesis of the disease.