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


CONCLUSIONS
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.
Silver
R M
RM
Department of Medicine, Medical University of South Carolina, Charleston 29425.
McKinley
K
K
Smith
E A
EA
Quearry
B
B
Harati
Y
Y
Sternberg
E M
EM
Heyes
M P
MP
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D016603:Eosinophilia-Myalgia Syndrome / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use; D007737:Kynurenine / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017378:Quinolinic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D012595:Scleroderma, Systemic / Q000378:metabolism / Q000628:therapy; D014364:Tryptophan / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D007737:Kynurenine; D007371:Interferon-gamma; D014364:Tryptophan; D017378:Quinolinic Acid