an observational cohort study of the kynurenine to tryptophan ratio in sepsis association with impaired immune and microvascular function一项观察性队列研究脓毒症的犬尿氨酸色氨酸比与免疫和微血管功能受损.pdfVIP

An Observational Cohort Study of the Kynurenine to Tryptophan Ratio in Sepsis: Association with Impaired Immune and Microvascular Function 1. 1,2. 1 1 3 Christabelle J. Darcy , Joshua S. Davis , Tonia Woodberry , Yvette R. McNeil , Dianne P. Stephens , Tsin W. Yeo1,2, Nicholas M. Anstey1,2* 1 Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia, 2 Division of Medicine, Royal Darwin Hospital, Darwin, Northern Territory, Australia, 3 Intensive Care Unit, Royal Darwin Hospital, Darwin, Northern Territory, Australia Abstract Both endothelial and immune dysfunction contribute to the high mortality rate in human sepsis, but the underlying mechanisms are unclear. In response to infection, interferon-c activates indoleamine 2,3-dioxygenase (IDO) which metabolizes the essential amino acid tryptophan to the toxic metabolite kynurenine. IDO can be expressed in endothelial cells, hepatocytes and mononuclear leukocytes, all of which contribute to sepsis pathophysiology. Increased IDO activity (measured by the kynurenine to tryptophan [KT] ratio in plasma) causes T-cell apoptosis, vasodilation and nitric oxide synthase inhibition. We hypothesized that IDO activity in sepsis would be related to plasma interferon-c, interleukin-10, T cell lymphopenia and impairment of microvascular reactivity, a measure of endothelial nitric oxide bioavailability. In an observational cohort study of 80 sepsis patients (50 severe and 30 non-severe) and 40 hospital controls, we determined the relationship between IDO activity (plasma KT ratio) and selected plasma cytokines, sepsis severity, nitric oxide-