Pathological and immunological effects of ingesting L-tryptophan and 1,1'-ethylidenebis (L-tryptophan) in Lewis rats.

Abstract

The eosinophilia-myalgia syndrome (EMS) has been associated with ingestion of L-tryptophan (L-TRP) produced by a single manufacturer. Epidemiological data implicated 1,1'-ethylidenebis(L-tryptophan) (EBT) (peak 97 or peak E) as a possible etiologic agent. We showed previously that Lewis rats treated with the L-TRP implicated in EMS develop fasciitis and perimyositis similar to those seen in human EMS. We now report the pathology associated with the treatment of Lewis rats with synthetic EBT and/or L-TRP. All animals treated for 6 wk with case-associated L-TRP or EBT developed significant myofascial thickening, compared with animals in the vehicle control and control L-TRP groups. However, even those animals receiving the control L-TRP showed a mild but significant increase in the thickness of the myofascia, compared with vehicle-treated control animals. All animals except vehicle controls also exhibited significant pancreatic pathology, including fibrosis and acinar changes. Only animals treated with case-associated L-TRP for 6 wk showed evidence of immune activation with increased frequency of CD8, Ia, and IL-2 receptor-positive cells in the peripheral blood. Animals receiving L-TRP or EBT for < 6 wk did not show significant differences in myofascial thickness, although these animals did show pancreatic acinar changes. Although these results demonstrate for the first time the pathological effects of EBT, they do not rule out the possibility that other impurities in the EMS-case-associated L-TRP may also contribute to some of the features of EMS. (J. Clin. Invest. 1993. 91:804-811.)

Toxicology and pharmacokinetics of 1-methyl-d-tryptophan: Absence of toxicity due to saturating absorption

“…Lewis rats receiving case-associated L-tryptophan developed fasciitis and perimyosits similar to the conditions observed in the human eosinophilia-myalgia syndrome (Crofford et al, 1990). Additional study showed that L-tryptophan induces some, but not all, of the pathology associated with chronic administration of case-associated Ltryptophan in Lewis rats (Love et al, 1993). Some of the associated pathology included significant myofascial thickening, pancreatic fibrosis, and acinar changes with increased CD8, Ia, and IL-2 receptor-positive cells in the peripheral blood.…”

Safety of 5-hydroxy-l-tryptophan

“…The authors concluded that the apparent morphologic and clinical similarities between these entities suggest that the animal model is suitable for further studying the pathogenesis of the gastrointestinal involvement in all these diseases. Further studies showed that direct feeding of synthetic EBT alone resulted in similar findings (Love et al, 1993). Silver et al (1994) used C57BI/6 mouse as a model.…”

Eosinophilia in Rheumatologic/Vascular Disorders

“…112 Lewis rats treated with one of these impurities, 1,1 0 -ethylidenebis (tryptophan) (EBT) or case-associated L-tryptophan, developed myofascial thickening similar to human EMS, but Lewis rats treated with L-tryptophan without EBT also showed mild myofascial thickening. 113 Another impurity, 3-(phenylamino) alanine, shares chemical properties with 3-(M-phenylamino)-1,2-propanediol, which was implicated as a causative agent of toxic oil syndrome in Spain in 1981. 114 …”