EXCRETION OF KYNURENIC ACID AND XANTHURENIC ACID DURING INFECTION

Abstract

Urinary excretion of diazotizable amines in acute febrile disease was demonstrated 90 years ago. These substances were subsequently identified as metabolites of tryptophan via the kynurenine pathway and the hepatic enzyme tryptophan pyrrolase (TP) was established as a regulator of this pathway. Animal studies have previously shown that TP has a circadian periodicity of activity and can be induced by gram-negative infections in the intact animal. Steroid administration also can enhance TP activity whereas endotoxin inhibits TP. This study measured urinary excretion of kynurenic acid (KA) and xanthurenic acid (XA), two tryptophan metabolites via the kynurenine pathway, in 26 hospitalized children with a variety of febrile disorders and 10 age-matched control subjects. Increased excretion of these metabolites was noted in the febrile patients and was unrelated to etiology of the fever. Circadian periodicity in the excretion of these metabolites was observed in both normal and febrile individuals. Significant group periodicity was not noted for minimal and maximal excretory values did not occur synchronously in patients within any group. Two patients with endotoxic shock failed to exhibit an increased excretion of kynuremic acid and xanthurenic acid presumably because of inhibition of TP. A biochemical basis for the therapeutic use of exogenous corticosteroids in endotoxic shock is postulated.