Trial reportJournal of neuroinflammation2021
Intravenous administration of LPS activates the kynurenine pathway in healthy male human subjects: a prospective placebo-controlled cross-over trial.
Trial report in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Possible Links Between Inflammation and Lipid Metabolism
Feasibility Study of Intra-Tumoral Lipopolysaccharide Immunotherapy for Intra-Abdominal Tumors
Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Feasibility of multimodal metabolic analysis for detecting early changes in acute neuroinflammation.Journal of neuroinflammation · 2026Article
- Behavioral, antioxidant, and kynurenine pathway modulation of a specific strain of Ligilactobacillus salivarius in a preclinical model of depression.European journal of nutrition · 2026Article
- The kynurenine pathway in depression and schizophrenia: convergent signals, divergent states, and clinical signatures.EXCLI journal · 2026Review
- Inflammatory models of depression in rodents and humans.Frontiers in psychiatry · 2026Review
- Tryptophan's Journey Through Pregnancy: The Role of Serotonin.International journal of tryptophan research : IJTR · 2026Review
- Pregnancy complications affect kynurenine pathway metabolite concentrations in umbilical cord blood.Reproductive biology and endocrinology : RB&E · 2025Article
- Metabolite and gut microbiota co-biomarkers in Danggui Shaoyao San: insights into a shared therapeutic approach.Frontiers in pharmacology · 2025Review
- Review
- Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axis.Frontiers in nutrition · 2025Review
- Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.Pharmacological reviews · 2024Review
- Gut-Brain Axis and Neuroinflammation: The Role of Gut Permeability and the Kynurenine Pathway in Neurological Disorders.Cellular and molecular neurobiology · 2024Review
- The improvement effect of exercise on rats with chronic stress-induced depression-like behavior: a discussion based on the kynurenine pathway.The Journal of international medical research · 2024Article
- Pathological shifts in tryptophan metabolism in human term placenta exposed to LPS or poly I:C†.Biology of reproduction · 2024Article
- Effects of Rumen-Protected L-Tryptophan Supplementation on Productivity, Physiological Indicators, Blood Profiles, and Heat Shock Protein Gene Expression in Lactating Holstein Cows under Heat Stress Conditions.International journal of molecular sciences · 2024Article
- Intestinal tryptophan metabolism in disease prevention and swine production.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2023Review
- Association between Tryptophan Metabolism and Inflammatory Biomarkers in Dairy Cows with Ketosis.Metabolites · 2023Article
- Melatonin and the Brain-Heart Crosstalk in Neurocritically Ill Patients-From Molecular Action to Clinical Practice.International journal of molecular sciences · 2022Review
- The Kynurenine Pathway and Polycystic Ovary Syndrome: Inflammation as a Common Denominator.International journal of tryptophan research : IJTR · 2022Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAdministration of lipopolysaccharide (LPS) from Gram-negative bacteria, also known as the human endotoxemia model, is a standardized and safe model of human inflammation. Experimental studies have revealed that peripheral administration of LPS leads to induction of the kynurenine pathway followed by depressive-like behavior and cognitive dysfunction in animals. The aim of the present study is to investigate how acute intravenous LPS administration affects the kynurenine pathway in healthy male human subjects.
methodsThe present study is a prospective, single-blinded, randomized, placebo-controlled cross-over study to investigate the effects of intravenously administered LPS (Escherichia coli O113, 2 ng/kg) on tryptophan and kynurenine metabolites over 48 h and their association with interleukin-6 (IL-6) and C-reactive protein (CRP). The study included 10 healthy, non-smoking men (18-40 years) free from medication. Statistical differences in tryptophan and kynurenine metabolites as well as associations with IL-6 and CRP in LPS and placebo treated subjects were assessed with linear mixed-effects models.
resultsSystemic injection of LPS was associated with significantly lower concentrations of plasma tryptophan and kynurenine after 4 h, as well as higher concentrations of quinolinic acid (QUIN) after 48 h compared to the placebo injection. No differences were found in kynurenic acid (KYNA) or picolinic acid plasma concentrations between LPS or placebo treatment. The KYNA/kynurenine ratio peaked at 6 h post LPS injection while QUIN/kynurenine maintained significantly higher from 3 h post LPS injection until 24 h. The kynurenine/tryptophan ratio was higher at 24 h and 48 h post LPS treatment. Finally, we report an association between the kynurenine/tryptophan ratio and CRP.
conclusionsOur findings strongly support the concept that an inflammatory challenge with LPS induces the kynurenine pathway in humans, activating both the neurotoxic (QUIN) and neuroprotective (KYNA) branch of the kynurenine pathway.
trial registrationThis study is based on a study registered at ClinicalTrials.gov, NCT03392701 . Registered 21 December 2017.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.