Studies of tryptophan metabolism in experimental animals and man during infectious illness

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Abstract
These studies provide reasonable, albeit indirect, evidence that tryptophan metabolism via the kynurenine pathway may have a diurnal or circadian rhythm, and that this rhythm may be analogous to the diurnal changes in hepatic tryptophan oxygenase activity previously observed in mice. Furthermore, our studies describe sequential changes in enzyme activity as they relate to the course of infection in man and may cast some light on the basic mechanisms accounting for increased enzyme activity. Increased excretion of kynurenine pathway metabolites in human infection seems consistent with adrenal glucocorticoid mediation of tryptophan oxygenase induction and may constitute an example of augmented hepatic protein synthesis occurring during infection. Such data, however, fail to provide any understanding of the role or importance of altered amino acid metabolism or protein synthesis in terms of host defense. Studies presently in progress are attempting to establish the extent of these changes and how they might bear on mechanisms of host resistance.