L-tryptophan implicated in human eosinophilia-myalgia syndrome causes fasciitis and perimyositis in the Lewis rat

• Published in: The Journal of clinical investigation Vol. 86; no. 5; pp. 1757 - 1763
• Main Authors: CROFFORD, L. J, RADER, J. I, ILLA, I, SMITH, C, STERNBERG, E. M, DALAKAS, M. C, HILL, R. H, PAGE, S. W, NEEDHAM, L. L, BRADY, L. S, HEYES, M. P, WILDER, R. L, GOLD, P. W
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01-11-1990
• Subjects: Animals; Biological and medical sciences; Brain Chemistry; Chromatography, High Pressure Liquid; Cortisone - blood; Disease Models, Animal; Drug toxicity and drugs side effects treatment; Eosinophilia - chemically induced; Fasciitis - chemically induced; Female; Humans; Kynurenine - blood; Medical sciences; Muscular Diseases - chemically induced; Myositis - chemically induced; Nucleic Acid Hybridization; Pharmacology. Drug treatments; Rats; Rats, Inbred Lew; RNA, Messenger - analysis; Syndrome; Tryptophan - toxicity; Experimental disease; Treatment; Toxicity; Animal; Etiopathogenesis; Hypophysoadrenal axis; Tryptophan; Complex syndrome
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci114902

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.