Tryptophan metabolism during infectious illness in man.

Widespread alterations occur in the metabolism of amino acids of the host during an infectious illness, but little is known about the specific changes. Tryptophan, a subject of a variety of studies, is unique in that its metabolites contribute to the diazo reaction [1]. Ehrlich [2] reported strongly positive diazo reactions during typhoid fever, and the test was used widely in the diagnosis of this infection before the era of bacterial identification [3]; in fact, it is still recommended as a useful test in the diagnosis of typhoid fever in underdeveloped regions [4]. Altered metabolism of tryptophan has been observed in other infectious illnesses [5-8]. In studies reported by Berry and Smythe [9], it was shown that tryptophan oxidase (TO), the hepatic enzyme which may limit the rate of tryptophan metabolism via the kynurenine pathway, exhibited reduced activity in mice during experimental infection with Salmonella typhimurium. Depression of TO activity was also reported during overwhelming staphylococcal infection [5]. While similar depression of TO activity occurred late in the course of pneumococcal septicemia in mice, a significant induction of the enzyme was noted during the incubation period of infection [10]. Altered tryptophan metabolism has also been implicated in the pathogenesis of endotoxin shock in experimental animals [11]. It seemed, therefore, appropriate to investigate the relationship between enzymatic degradation of tryptophan and the clinical responses in man during the course of several different infectious illnesses.