A community-based study on determinants of circulating markers of cellular immune activation and kynurenines: the Hordaland Health Study

Abstract

SummaryCirculating neopterin and kynurenine/tryptophan ratio (KTR) increase during inflammation and serve as markers of cellular immune activation, but data are sparse on other determinants of these markers and metabolites of the kynurenine pathway. We measured neopterin, tryptophan, kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid in plasma in two age groups, 45-46 years (n = 3723) and 70-72 years (n = 3329). Differences across categories of the potential determinants, including age, gender, renal function, body mass index (BMI), smoking and physical activity, were tested by Mann-Whitney U-test and multiple linear regression including age group, gender, renal function and lifestyle factors. In this multivariate model, neopterin, KTR and most kynurenines were 20-30% higher in the older group, whereas tryptophan was 7% lower. Men had 6-19% higher concentrations of tryptophan and most kynurenines than women of the same age. Compared to the fourth age-specific estimated glomerular filtration rate (eGFR) quartile, the first quartile was associated with higher concentrations of neopterin (25%) and KTR (24%) and 18-36% higher concentrations of kynurenines, except 3-hydroxyanthranilic acid. Additionally, KTR, tryptophan and all kynurenines, except anthranilic acid, were 2-8% higher in overweight and 3-17% higher in obese, than in normal-weight individuals. Heavy smokers had 4-14% lower levels of tryptophan and most kynurenines than nonsmokers. Age and renal function were the strongest determinants of plasma neopterin, KTR and most kynurenines. These findings are relevant for the design and interpretation of studies investigating the role of plasma neopterin, KTR and kynurenines in chronic diseases.

Influence of Cut-Points to Measure and Classify the Physical Activity Level of Older Adults

“…A prevalência de ativos no contexto geral foi de 73,9% no estudo de Zaitune et al 25 e 84,9% no estudo de Azevedo et al 26 ambos realizados em São Paulo; de 59,3% em idosos de Florianópolis 27 , de 58% em pesquisa desenvolvida nas regiões Sul e Nordeste do Brasil 28 e de 22,3 a 37,7% nos dados levantados via Vigitel 4 . Dados internacionais demonstraram que, das 1860 idosas que compunham a amostra do Hordaland Health Study, 43% delas realizavam pelo menos uma hora de atividades físicas moderadas e vigorosas por dia 29 . A explicação para essas diferenças pode estar na metodologia adotada.…”

Evaluation of Tryptophan Metabolism in Chronic Immune Activation

“…In this regard, a causal relationship is evident between the Trp metabolism and immune defi ciency in elderly. Thus, neopterin, Kyn-Trp ratio, and all Kyn metabolites are 20-30 % higher in the older group, whereas Trp is 7 % lower (Theofylaktopoulou et al 2013 ). Eventually, the reduced serum Trp concentrations and increased Kyn levels indicate increased chronic low-grade infl ammation in elderly.…”

“…Impaired satiety due to subsequent insuffi cient serotonin synthesis causes overfeeding and obesity (Brandacher et al 2007 ). Kyn-Trp ratio and all kynurenines, except anthranilic acid, are 2-8 % higher in overweight and 3-17 % higher in obese, than in normalweight individuals (Theofylaktopoulou et al 2013 ). Bariatric surgery signifi cantly diminishes immune mediators by substantial weight reduction.…”

3-Hydroxykynurenic Acid and Type 2 Diabetes: Implications for Aging, Obesity, Depression, Parkinson’s Disease, and Schizophrenia

“…KTR, a marker of the rate of KYN formation from TRP, increased with aging in humans when comparing three age groups (34-60, 61-71, and 72-93 years) (Frick et al 2004 ) and nonagenarians with 45-year-old subjects (Pertovaara et al 2006 ). Increased formation of KYNA was observed in aged rat brain (Moroni et al 1988 ;Gramsbergen et al 1992 ) and in human serum (Urbanska et al 2006 ;Theofylaktopoulou et al 2013 ). The higher rate of TRP conversion into KYN at the entry into the study was predictive of higher mortality in 10-year prospective study of nonagenarians (Pertovaara et al 2007 ).…”

“…Neopterin levels increased with age Pertovaara et al 2006 ;Theofylaktopoulou et al 2013 ;Spencer et al 2010 ) with no gender differences (Schennach et al 2002 ), while age-associated increase of IDO was more prominent in women than in men (Raitala et al 2005 ). Elevation of neopterin, as a consequence of upregulation of IFNG production, has been shown to correlate with several components of infl ammation-associated metabolic syndrome, including IR in populations of European ancestry (Grammer et al 2009 ).…”