Activated Immune System and Inflammation in Healthy Ageing: Relevance for Tryptophan and Neopterin Metabolism

Abstract

Immune activation not only accompanies inflammation in various disorders including infections, autoimmune syndromes and cancer, but it also represents a characteristic feature of ageing. Immune deviations which are most widely expressed in the elderly include increased neopterin production and tryptophan breakdown. These biochemical events result from the activation of the immune system and are preferentially triggered by pro-inflammatory stimuli, such as the Th1-type cytokine interferon-γ. They seem to play a role in the development of several age-related disorders and might be involved in the pathogenesis of common symptoms, including neurobehavioral disorders (e.g., cognitive and mood disturbances), anemia, cachexia, weight-loss but also immunodeficiency. Concentrations of the biomarkers neopterin and Kyn/Trp were found to be predictive of overall disease specific mortality in coronary artery disease, infections and various types of cancer. Immune activation and inflammation are also accompanied by high output of reactive oxygen species and thereby may lead to the development of oxidative stress and contribute to the vitamin deficiency which is often observed in the elderly. Accordingly, increases in neopterin were found to correlate with a substantial decline in key vitamins, including folate and vitamin-B6, - B12, -C, -D and -E.

Serum Levels of High-sensitivity C-Reactive Protein at Admission Are More Strongly Associated with Poststroke Depression in Acute Ischemic Stroke than Homocysteine Levels

“…Another inflammatory pathway by which cytokines may mediate behavioral effects is by activation of IDO [41], an enzyme expressed in multiple cell types, including macrophages, dendritic cells, microglia, astrocytes, and neurons [42]. Second, immune activation and inflammation are also accompanied by high output of reactive oxygen species and thereby may lead to the development of oxidative stress and contribute to the vitamin deficiency which is often observed in the elderly [43]. Inflammation and oxidative stress are inextricably connected in physiologic as well as disease states.…”

The relationship between high‐sensitivity C‐reactive protein at admission and post stroke depression: a 6‐month follow‐up study

“…Other special mechanism should be considered. Second, immune activation and inflammation are also accompanied by high output of reactive oxygen species and thereby may lead to the development of oxidative stress and contribute to the vitamin deficiency which is often observed in the elderly (Capuron et al, 2014). It is suggested that these changes may reflect the increase in the concentration of pro-inflammatory cytokines and other inflammatory mediators such as PG-E2 and nitric oxide whose synthesizing enzymes are also induced by these cytokines (Howren et al, 2009).…”

One‐carbon metabolite ratios as functional B‐vitamin markers and in relation to colorectal cancer risk

“…To further evaluate the specificity of the ratio‐based B‐vitamin markers in relation to total B‐vitamin status and not as markers of kidney dysfunction and inflammation, we calculated a combined measure of kidney dysfunction and inflammation by summing log‐transformed standardized plasma concentrations of the sensitive kidney function marker SDMA, and the inflammatory markers KTR and neopterin . The score was then used in ROC analysis by defining a dichotomous kidney dysfunction and inflammation variable using the highest 95 percentile of the score in controls as the cut‐off.…”