Inflammation-associated changes in the cellular availability of tryptophan and kynurenine in renal transplant recipients

Abstract

In the course of evaluating the hypothesis that tryptophan or tryptophan metabolites mediate some of the physiological or pathological aspects of the inflammatory response, we assessed the bioavailability of tryptophan and kynurenine in renal allograft recipients during periods of stable graft function, acute rejection and OKT3 therapy. In normal controls and patients with stable function, approximately 8% of the tryptophan and less than 5% of the kynurenine in serum were present in the freely diffusable form. The free tryptophan concentration was significantly increased during acute rejection, while free tryptophan as well as total and free kynurenine concentrations were significantly increased during OKT3 therapy. In each case the ratio of free indole to the sum of the plasma concentrations of large neutral amino acids was also increased. In vitro studies of indole binding to human serum proteins demonstrated the parallel displacement of bound tryptophan and kynurenine by physiological changes in pH, serum albumin concentration and free fatty acid concentration. The results suggest that inflammation associated increases in the oxidative metabolism of tryptophan are accompanied by the increased availability of serum indoles for intracellular metabolism in the tissues.