The L-tryptophan eosinophilia myalgia syndrome occurred in epidemic proportions in association with contaminated L-tryptophan. We first described this syndrome and studied its biochemistry in humans in relation to L-5-hydroxytryptophan in 1980 and again in relation to L-tryptophan in 1990. We have established an animal model for this syndrome in Lewis (LEW/N) rats, and have determined that one of the impurities, (EBT), causes fascial thickening and together with pure L-- tryptophan, causes peripheral blood mononuclear cell activation in LEW/N rats. Both EBT and contaminated L-TRP were associated with significant suppression of hypothalamic CRH mRNA expression, compared to rats treated with pure L-TRP or vehicle control. Furthermore, pure L-tryptophan itself, as well as contaminated L-TRP and EBT, cause pancreatic fibrosis in LEW/N rats. Thus, pure tryptophan contributes to some of the features of the syndrome, but alone does not cause its characteristic features. The breakdown product of this impurity, a tetrahydro-beta-carbolene, exerts variable effects on neuronal survival, depending on the stage of maturation of the cells. It is toxic to mature neurons, and prevents naturally occurring cell death in immature cultures, in a dose-related, stereospecific manner, suggesting that it exerts these effects through a receptor mediated mechanism. The neurotoxicity is dependent on IL-1. Taken together, L-TRP EMS may be viewed as a toxic syndrome in which a neurotransmitter-related molecule may both induce inflammatory disease, and amplify inflammation indirectly through suppression of the HPA axis.
