Tryptophan metabolism via the kynurenine pathway in patients with the eosinophilia-myalgia syndrome.

Abstract

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 less than 0.05) and in asymptomatic users of LT (n = 5; P less than 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 less than 0.05), normal subjects (P less than 0.02), and asymptomatic users of LT (P less than 0.05). EMS patients also had significantly elevated levels of L-kynurenine (P less than 0.05) and quinolinic acid (P less than 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.

• Authors: R M Silver, K McKinley, E A Smith, B Quearry, Y Harati, E M Sternberg, M P Heyes
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 35 Issue 9 Pg. 1097-105 (Sep 1992) ISSN: 0004-3591 [Print] United States
• PMID: 1418026 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adrenal Cortex Hormones
• Kynurenine
• Interferon-gamma
• Tryptophan
• Quinolinic Acid

Topics

• Adrenal Cortex Hormones (therapeutic use)
• Adult
• Aged
• Eosinophilia-Myalgia Syndrome (drug therapy, metabolism)
• Female
• Humans
• Interferon-gamma (therapeutic use)
• Kynurenine (blood, cerebrospinal fluid, metabolism)
• Male
• Middle Aged
• Quinolinic Acid (blood, cerebrospinal fluid)
• Scleroderma, Systemic (metabolism, therapy)
• Tryptophan (blood, cerebrospinal fluid, metabolism)