1,1'-Ethylidenebis[tryptophan] induces pathologic alterations in muscle similar to those observed in the eosinophilia-myalgia syndrome

Neurology. 1994 Dec;44(12):2390-2. doi: 10.1212/wnl.44.12.2390.

Abstract

1,1'-Ethylidenebis[tryptophan] (EBT), a derivative of L-tryptophan (LT), is a trace contaminant in batches of LT implicated by epidemiologic evidence in the pathogenesis of the eosinophilia-myalgia syndrome (EMS). We treated female Lewis rats with EBT or unimplicated LT (4 mg per 100 grams daily) by intraperitoneal injection. No rash or weakness occurred in either group. All three EBT rats had a few necrotic muscle fibers. In two rats, perimysium and fascia were abnormally thickened and infiltrated with lymphocytes, macrophages, and sparse eosinophils; two rats had sparse perineurial inflammatory cells. Rats treated with unimplicated LT showed no abnormality. These findings replicate an important feature of human EMS and support the epidemiologic evidence linking EBT to the pathogenesis of the human disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Eosinophilia-Myalgia Syndrome / chemically induced*
  • Eosinophilia-Myalgia Syndrome / pathology
  • Female
  • Macrophages / drug effects
  • Macrophages / pathology
  • Microcirculation / drug effects
  • Microcirculation / pathology
  • Microcirculation / ultrastructure
  • Muscles / blood supply
  • Muscles / drug effects
  • Muscles / pathology*
  • Rats
  • Rats, Inbred Lew
  • Time Factors
  • Tryptophan / analogs & derivatives*
  • Tryptophan / toxicity

Substances

  • 1,1'-ethylidene bis(tryptophan)
  • Tryptophan