EOSINOPHIL-ACTIVE CYTOKINE FROM MONONUCLEAR-CELLS CULTURED WITH L-TRYTOPHAN PRODUCTS - AN UNEXPECTED CONSEQUENCE OF ENDOTOXIN CONTAMINATION

Background: The eosinophilia-myalgia syndrome, caused by a contaminant or contaminants in epidemiologically implicated L-tryptophan products , is characterized by eosinophilia and eosinophil degranulation. We hy pothesized that immune cells are stimulated by implicated L-tryptophan and produce eosinophil-active cytokines. Objectives: This study was d esigned to identify substances in L-tryptophan causing the eosinophili a-myalgia syndrome. Methods: Peripheral blood mononuclear cells were c ultured with L-trptophan products, and supernatants were tested for th eir ability to enhance eosinophil degranulation and survival in vitro and for their cytokine content. Subsequently, 46 different L-tryptopha n lots were analyzed for their in vitro biologic activities. Results: After peripheral blood mononuclear cells were cultured with implicated L-tryptophan, their supernatants enhanced eosinophil degranulation an d survival. These activities were blocked by anti-granulocyte-macropha ge colony-stimulating factor (GM-CSF) antibody; immunoreactive GM-CSF was measurable in the supernatants. Monocytes, but not T lymphocytes, were the responding cells. However, no correlation was observed betwee n the in vitro biologic activity and lots of epidemiologically implica ted L-tryptophan products. This biologic activity in the L-tryptophan products was characterized as endotoxin. Conclusion: Although L-trypto phan products stimulate peripheral blood mononuclear cells to produce GM-CSF, this response is caused by endotoxin contamination of the L-tr yptophan products and not by a specific L-tryptophan contaminant. Endo toxin contamination must be considered as a possible cause of eosinoph il-active cytokine production by peripheral blood mononuclear cells.