The following is a summary of “Lipopolysaccharide-induced changes in the kynurenine pathway and symptoms of sickness behavior in humans,” published in the July 2023 issue of Psychoneuroendocrinology by Balter et al.

Metabolites originating from the kynurenine pathway are postulated to be potentially involved in depression associated with inflammation. However, more human experimental studies need to evaluate the dynamics of kynurenine metabolites in sickness induced through experimentation. The objective of the current investigation was to evaluate alterations in the kynurenine pathway and investigate its correlation with indications of sickness behavior during a sudden experimental immune challenge. This clinical trial involved 22 individuals who were in good health. The study followed a double-blind, placebo-controlled, randomized cross-over design. The participants, with an average age of 23.4 years and a standard deviation of 3.6, included nine women. During two separate sessions, they were administered an intravenous injection of lipopolysaccharide (LPS) at a dosage of 2.0 ng/kg and a saline solution (placebo). 

The order in which the injections were given was randomized. Hematological specimens (0 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 7 hours post-injection) were examined for kynurenine metabolites and inflammatory cytokines. The severity of symptoms of sickness behavior was evaluated using the 10-item Sickness Questionnaire at 0 hours, 1.5 hours, 3 hours, 5 hours, and 7 hours after the injection. Lipopolysaccharide (LPS) administration resulted in notable reductions in plasma tryptophan levels at 2 hours, 4 hours, 5 hours, and 7 hours after injection. Similarly, kynurenine concentrations were significantly lower at 2 hours, 3 hours, 4 hours, and 5 hours post-injection. Nicotinamide levels were also decreased at 4 hours, 5 hours, and 7 hours after injection. Conversely, quinolinic acid levels were higher at 5 hours post-injection compared to the placebo. Lipopolysaccharide (LPS) did not impact the levels of kynurenic acid, 3-hydroxykynurenine, and picolinic acid. 

The onset of the pathological symptoms exhibited a predominantly uniform pattern across various indicators, peaking at approximately 1.5 to 3 hours following the administration of the injection. Alterations in plasma concentrations of kynurenine metabolites appear concurrently rather than preceding or succeeding fluctuations in subjective illness. Preliminary examinations reveal that elevated Sickness Questionnaire aggregate scores at 1.5–5 hours after injection negatively correlated with kynurenic acid and nicotinamide levels. These findings provide additional evidence for alterations in the kynurenine pathway induced by LPS. Still, it is unclear whether they directly contribute to the acute symptoms of sickness behavior associated with LPS, as inferred from blood levels. Future medical research may consider a larger sample size to examine further the role of the kynurenine pathway in the sickness response.

Source: sciencedirect.com/science/article/pii/S0306453023000884