1,1'-ETHYLIDENEBIS(TRYPTOPHAN) (PEAK-E) INDUCES FUNCTIONAL ACTIVATION OF HUMAN EOSINOPHILS AND INTERLEUKIN-5 PRODUCTION FROM T-LYMPHOCYTES - ASSOCIATION OF EOSINOPHILIA-MYALGIA-SYNDROME WITH A L-TRYPTOPHAN CONTAMINANT

This study was designed to clarify the important association between eosinophilia-myalgia syndrome (EMS) and the L-tryptophan contaminant, ''Peak E.'' To determine the functional activation of eosinophils induced by Peak E, eosinophil cationic protein (ECP) release was examined. Peak E augmented the release of ECP from peripheral blood normodense eosinophils by degranulation. Proliferative analysis using the human eosinophilic leukemia cell line EoL-3 showed prominent cellular replication in the presence of Peak E. Moreover, Peak E upregulated interleukin 5 (IL-5) receptor levels on normodense eosinophils. Of particular interest, Peak E-stimulated human splenic T cells produced bioactive and immunoreactive IL-5. Marked induction of IL-5 mRNA in Peak E-stimulated T cells was also shown by reverse transcriptase polymerase chain reaction (RT-PCR). In contrast, L-tryptophan without the contaminant showed none of these effects. Thus, these data suggest that Peak E might be involved in the pathogenesis of EMS through bimodal mechanism including IL-5 generation by T cells and potentiation of eosinophil functional activation.