1,1'-ETHYLIDENEBIS[L-TRYPTOPHAN], AN IMPURITY IN L-TRYPTOPHAN ASSOCIATED WITH EOSINOPHILIA-MYALGIA-SYNDROME, STIMULATES TYPE-I COLLAGEN GENE-EXPRESSION IN HUMAN FIBROBLASTS IN-VITRO

Eosinophilia-myalgia syndrome (EMS), a recently described inflammatory disorder characterized by myalgia, peripheral eosinophilia, and multi system inflammation is associated with L-tryptophan consumption. Fibro sis of various tissues due to excessive accumulation of type I collage n is a prominent late manifestation of the syndrome. 1,1'-Ethylidenebi s [L-tryptophan] (EBT), an impurity distinct from L-tryptophan found i n case-associated lots, has been implicated in the pathogenesis of EMS . We therefore investigated the effects of EBT on normal human fibrobl ast function in vitro. Incubation of confluent fibroblasts with EBT, b ut not its hydrolysis product 1-methyl-tetrahydro-beta-carboline-3-car boxylic acid, caused a dose-dependent increase in collagen synthesis a nd in type I collagen mRNA levels independent of its effect on prolife ration. In contrast, expression mRNA for fibronectin was not affected. These findings indicate that EBT stimulates type I collagen productio n by human fibroblasts, and suggest that EBT may be involved in the de velopment of fibrosis in EMS.