Histopathologic Studies of Muscle and Peripheral Nerve Following Ingestion of L-tryptophan in Rats

ABSTRACT

The eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan in man is defined by the CDC(1989) as follows 1) eosinophil count more than 1,000 cells per microliter; 2) generalized myaligia(at some point during the course of illness) of severity sufficient to affect a patient's ability to pursue his or her usual daily activities; 3) no evidence of any infection(e.g., trichinosis) or neoplasm that would explain either the eosinophila or the myalgia. The pathologic findings of the eosinophilia-myalgia syndrome varies according to the degree of severity and types of inflammatory cells in the skeletal muscle. In order to simulate this syndrome in animals and further determine its histopathogenesis, L-tryptophan was administered to rats in the laboratory at various doses(25 mg/kg, 50 mg/kg, 150 mg/kg) over a set period of time. In this study, positive histopathologic findings were designated according to the inflammatory cell infiltration of the epimysium and epineurium. Most of the pathologic findings in the positive group were that of inflammatory cell infiltration composed mainly of eosinophils in the epimysial, epineurial connective and surrounding adipose tissues. Only a few necrotic muscle fibers were seen, and there was absence of any evidence of inflammatory cell inflitration in endoneurium or axonal degenerations. Of 59 rats which were given L-tryptophan, 27 rats(45.8%) met the criteria and were designated as belongintg to the positive group. Only 2 rats ingested with L-tryptophan(150 mg/kg) for 2 months and 4 months showed an eosinophil count more than 1,000 cells/microliter. The eosinophil count in the positive group showed significantly different levels when compared to the the negative group and control group. On the other hand, there were no significant differences in the electrodiagnostic study and serum CK, SGOT, SGPT level between the positive, negative and control groups. In summary, histopathologic findings similar to the eosinophilia-myalgia syndrome were inducible in rats followign the administration of L-tryptophan.