L-tryptophan implicated in human eosinophilia-myalgia syndrome causes fasciitis and perimyositis in the Lewis rat.
Tryptophan-associated eosinophilia-myalgia syndrome (L-TRP-EMS) is a newly described syndrome which occurred in epidemic fashion in the United States in the summer and fall of 1989. Epidemiologic data has linked the syndrome to intake of L-tryptophan (L-TRP) from one specific manufacturer, but the precise etiologic compound(s) must be established by replication of the syndrome in an appropriate animal model. In this study, implicated L-TRP, United States Pharmacopeia (USP) grade L-TRP, or vehicle was administered by gavage in a blinded fashion for 38 d to female Lewis rats at doses comparable with those ingested by patients who developed the eosinophilia-myalgia syndrome. Animals receiving implicated L-TRP, but not those receiving USP grade L-TRP or vehicle, developed histologic signs consistent with fasciitis and perimyositis, specific pathologic features of human L-TRP-EMS. Peripheral blood eosinophilia was not observed. Hypothalamic corticotropin releasing hormone mRNA levels were lower and plasma corticosterone levels tended to be lower in the animals that received implicated L-TRP. Plasma L-kynurenine was higher in both L-TRP-treated groups compared to the vehicle-treated animals. The female Lewis rat is known to be susceptible to a wide variety of inflammatory diseases. Identification of specific inflammatory changes in this rat following exposure to implicated L-TRP indicates that this animal model will be important in subsequent investigations into the etiology, pathogenesis, and treatment of human L-TRP-EMS.
Crofford
L J
LJ
National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892.
Rader
J I
JI
Dalakas
M C
MC
Hill
R H
RH
Page
S W
SW
Needham
L L
LL
Brady
L S
LS
Heyes
M P
MP
Wilder
R L
RL
Gold
P W
PW
D000818:Animals; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D003348:Cortisone / Q000097:blood; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000139:chemically induced; D005208:Fasciitis / Q000139:chemically induced*; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000097:blood; D009135:Muscular Diseases / Q000139:chemically induced; D009220:Myositis / Q000139:chemically induced*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D013577:Syndrome; D014364:Tryptophan / Q000633:toxicity*
D012333:RNA, Messenger; D007737:Kynurenine; D014364:Tryptophan; D003348:Cortisone