Eosinophil-active cytokine from mononuclear cells cultured with L-tryptophan 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 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.
Kita
H
H
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Mayeno
A N
AN
Weyand
C M
CM
Goronzy
J J
JJ
Weiler
D A
DA
Lundy
S K
SK
Abrams
J S
JS
Gleich
G J
GJ
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
D016207:Cytokines; D004731:Endotoxins; D014364:Tryptophan