Alterations in tryptophan metabolism in the toxic oil syndrome and in the eosinophilia-myalgia syndrome.

The eosinophilia-myalgia syndrome (EMS) was associated with ingestion of L-tryptophan containing products and was accompanied by altered metabolism of L-tryptophan during the active phase. Many patients with EMS exhibited clinical and histopathological features similar to another epidemic, the toxic oil syndrome (TOS), associated with ingestion of adulterated rapeseed oil. We hypothesized that patients with TOS, like patients with EMS, may have had altered metabolism of L-tryptophan during the acute phase of the illness. Therefore, we quantitated the tryptophan metabolites, L-kynurenine and quinolinic acid, and we measured neopterin, a marker of interferon-gamma (IFN-gamma), in blood obtained during the acute phase of each syndrome. Patients with TOS or EMS had significantly higher L-kynurenine and quinolinic acid than healthy control subjects or rheumatic disease control subjects. Neopterin was also elevated in patients with untreated TOS and EMS, and correlated strongly with L-kynurenine and quinolinic acid. Our data suggest that indoleamine-2,3-dioxygenase (IDO), the rate limiting enzyme of the kynurenine pathway of L-tryptophan metabolism, was activated in both syndromes by cytokines including IFN-gamma, and that perhaps products of tryptophan metabolism played a role in the pathogenesis of EMS and TOS.