title: Eosinophil-active cytokine from mononuclear cells cultured with L-tryptophan products: an unexpected consequence of endotoxin contamination.
abstract: 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 hypothesized that immune cells are stimulated by implicated L-tryptophan and produce eosinophil-active cytokines.
  
  
  OBJECTIVE
  This study was designed to identify substances in L-tryptophan causing the eosinophilia-myalgia syndrome.
  
  
  METHODS
  Peripheral blood mononuclear cells were cultured with L-tryptophan products, and supernatants were tested for their ability to enhance eosinophil degranulation and survival in vitro and for their cytokine content. Subsequently, 46 different L-tryptophan 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 and survival. These activities were blocked by anti-granulocyte-macrophage 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 between the in vitro biologic activity and lots of epidemiologically implicated L-tryptophan products. This biologic activity in the L-tryptophan products was characterized as endotoxin.
  
  
  CONCLUSIONS
  Although L-tryptophan products stimulate peripheral blood mononuclear cells to produce GM-CSF, this response is caused by endotoxin contamination of the L-tryptophan products and not by a specific L-tryptophan contaminant. Endotoxin contamination must be considered as a possible cause of eosinophil-active cytokine production by peripheral blood mononuclear cells.
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kita
authors.forename: A N
authors.initials: AN
authors.lastname: Mayeno
authors.forename: C M
authors.initials: CM
authors.lastname: Weyand
authors.forename: J J
authors.initials: JJ
authors.lastname: Goronzy
authors.forename: D A
authors.initials: DA
authors.lastname: Weiler
authors.forename: S K
authors.initials: SK
authors.lastname: Lundy
authors.forename: J S
authors.initials: JS
authors.lastname: Abrams
authors.forename: G J
authors.initials: GJ
authors.lastname: Gleich
mesh_terms: D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis*; D004731:Endotoxins / Q000737:chemistry; D016603:Eosinophilia-Myalgia Syndrome / Q000097:blood* / Q000276:immunology; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D014364:Tryptophan / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology
chemical_list: D016207:Cytokines; D004731:Endotoxins; D014364:Tryptophan