Therefore, the plasma kynurenine/tryptophan ratio (KTR) is this website influenced by the activities of both IDO and TDO, while plasma neopterin reflects only IFN-γ activity [4]. More than 90% of Trp is metabolized through the kynurenine pathway to compounds collectively named kynurenines [3]. After the

rate-limiting conversion of Trp to Kyn, Kyn is metabolized further to anthranilic acid (AA), kynurenic acid (KA) or 3-hydroxykynurenine (HK), which is converted to either 3-hydroxyanthranilic acid (HAA) or xanthurenic acid (XA) (Fig. 1). Both neopterin [5] and KTR [6] have been found to be associated with chronic diseases. A number of kynurenines, such as Kyn, HK, HAA and KA, have been reported to play a role ABT-737 solubility dmso in immune regulation [7]. Additionally, several kynurenines have been associated with autoimmune diseases [6], infection [6], cancer [6], neuroendocrine disorders [8] and metabolic syndrome [8]. In studies examining the relation of these markers and metabolites to disease outcomes, it is important to be aware of their potential determinants in order to account for possible confounding. Data on variations in neopterin, KTR and kynurenines according to age [9-13], gender [12-15], renal function [16-18], overweight/obesity [19-23] and smoking [9, 15] are sparse or fragmentary, while data on the potential effects of physical activity are lacking. A thorough investigation

of the importance of such factors is motivated by the considerable renal clearance of kynurenines [17], the increased IFN-γ activity accompanying obesity [4], the anti-inflammatory effect of physical activity [24] and the known immunomodulatory effects of smoking [25]. We therefore

investigated age, gender, renal function, body mass index (BMI), smoking and physical activity as determinants of neopterin, KTR and kynurenines in a large community-based cohort of middle-aged and elderly men and women. The source population consisted of subjects born in 1925–27 or 1950–51 and residing in the city of Bergen (Norway) or the neighbouring suburban municipalities (n = 9187) who participated in the Hordaland Health Study (HUSK) during 1997–99. The overall attendance rate was 77%, providing all a sample of 7052 participants in the age groups 46–47 years (2062 women and 1661 men) and 70–72 years of age (1860 women and 1469 men). HUSK is a collaboration between the National Health Screening Service, University of Bergen, University of Oslo and local health services in the Bergen area. The study protocol was approved by the Western Norway Regional Committee for Medical Research Ethics and by the Norwegian Data Inspectorate. All participants gave written informed consent. Non-fasting blood samples were collected into tubes containing ethylenediamine tetraacetic acid (EDTA) and stored at 4–5°C within 15–30 min.