Inverse association between serum selenium concentrations and parameters of immune activation in patients with cardiac disorders
As a component of the enzyme glutathione peroxidase, the essential trace element selenium contributes to the reduction of peroxides. Disturbed selenium availability may relate to an activated immune response. In humans, immune activation is reflected by increased neopterin production and accelerated tryptophan degradation, expressed as the kynurenine to tryptophan ratio (kyn/trp). Th1-type cytokine interferon-gamma induces both these immunobiological events in human macrophages and they are often activated in patients with cardiac disorders. The aim of this study was to determine the relationship between serum selenium concentrations and neopterin production and tryptophan degradation in patients with cardiac disorders.
In 56 patients (28 females) with cardiac disorders, serum selenium concentrations were determined by graphite-furnace atomic absorption spectrometry. Serum neopterin concentration was measured by ELISA and tryptophan degradation was examined by HPLC.
Selenium concentrations were in the range 0.41-1.90 micromol/L (median 1.02) and were well within the local normal range. Approximately two-thirds of patients presented with higher neopterin concentrations (median 16.4 nmol/L) and tryptophan degradation (median 57 micromol/mmol kyn/trp). There was an inverse correlation between serum selenium and kyn/trp (Spearman's rank correlation, r(s)=-0.431; p<0.001) and neopterin concentrations (r(s)=-0.300; p<0.05). Neopterin concentrations correlated strongly with kyn/trp (r(s)=0.712; p<0.0001).
A higher degree of tryptophan degradation and of neopterin production in patients with cardiac disorders coincides with lower, albeit still normal, serum selenium concentrations. Data show that in these patients immune activation is associated with lower serum selenium concentrations.
Available from: Bernadette Stang
- "When produced in excess, ROS are important mediators of cell and tissue injury. Because Se is involved in redox reactions, and immune activation is usually associated with increased production of ROS by cells of the immune system, higher Se may help suppress tissue damage caused by ROS (reviewed in Murr et al. ). As a component of the glutathione peroxidase family of enzymes, Se contributes to the reduction of hydroperoxides in cells. "
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ABSTRACT: ABSTRACT: We reported previously that sheep affected with footrot (FR) have lower whole-blood selenium (WB-Se) concentrations and that parenteral Se-supplementation in conjunction with routine control practices accelerates recovery from FR. The purpose of this follow-up study was to investigate the mechanisms by which Se facilitates recovery from FR. Sheep affected with FR (n = 38) were injected monthly for 15 months with either 5 mg Se (FR-Se) or saline (FR-Sal), whereas 19 healthy sheep received no treatment. Adaptive immune function was evaluated after 3 months of Se supplementation by immunizing all sheep with a novel protein, keyhole limpet hemocyanin (KLH). The antibody titer and delayed-type hypersensitivity (DTH) skin test to KLH were used to assess humoral immunity and cell-mediated immunity, respectively. Innate immunity was evaluated after 3 months of Se supplementation by measuring intradermal responses to histamine 30 min after injection compared to KLH and saline, and after 15 months of Se supplementation by isolating neutrophils and measuring their bacterial killing ability and relative abundance of mRNA for genes associated with neutrophil migration. Compared to healthy sheep, immune responses to a novel protein were suppressed in FR-affected sheep with smaller decreases in FR-affected sheep that received Se or had WB-Se concentrations above 250 ng/mL at the time of the immune assays. Neutrophil function was suppressed in FR-affected sheep, but was not changed by Se supplementation or WB-Se status. Sheep FR is associated with depressed immune responses to a novel protein, which may be partly restored by improving WB-Se status (> 250 ng/mL).
Available from: Andreas Spittler
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ABSTRACT: Increased blood concentrations of phenylalanine in patients with trauma and sepsis are common but unexplained. We examined the potential relationship between serum concentrations of phenylalanine and the immune activation marker neopterin in 84 specimens of 18 patients (14 males and 4 females) post-trauma during 12–14 days of follow up. Compared to healthy controls, average phenylalanine and neopterin concentrations were elevated in patients, and there existed a positive correlation between concentrations of the two analytes (r
s = 0.375, p < 0.001). No such association existed between neopterin and tyrosine concentrations (r
s = −0.018), but neopterin concentrations correlated to the phenylalanine to tyrosine ratio (r
s = 0.328, p = 0.001).
Increased phenylalanine implies insufficient conversion by phenylalanine (4)-hydroxylase (PAH). Oxidative stress due to immune activation and inflammation may destroy cofactor 5,6,7,8-tetrahydrobiopterin and impair PAH activity. This assumption is further supported by the correlation found between higher neopterin concentrations and higher phenylalanine to tyrosine ratio, which estimates efficacy of PAH.
Available from: Walter Swardfager
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ABSTRACT: An increase in immune-stimulated synthesis of kynurenine from tryptophan by indoleamine 2,3-dioxygenase (IDO) has been observed in patients with coronary artery disease (CAD). However, neuropsychiatric correlates of IDO activation remain unexplored. We hypothesize that IDO activation, as measured by the kynurenine to tryptophan (K/T) ratio, is associated with depressive symptoms in those with CAD. This cross-sectional study recruited subjects with CAD (n=95) from a cardiac rehabilitation facility. Demographic, anthropometric and cardiac data were obtained by chart review. Patients using an antidepressant were excluded. The presence of a major depressive episode or minor depression was assessed using a structured clinical interview for depression based on Diagnostic and Statistical Manual 4th edition criteria. The Center for Epidemiological Studies-Depression Scale (CES-D) was used to quantify depressive symptoms. A standardized exercise stress test was used to assess cardiopulmonary fitness as summarized using the peak volume of oxygen consumption (Peak VO(2)). Kynurenine and tryptophan were assayed from fasting plasma samples to obtain the K/T ratio. Higher K/T ratios were significantly associated with higher CES-D scores (beta=.322, p=.002) in a linear regression controlling for time since most recent acute coronary syndrome (tACS), age and sex. Twenty-four patients met criteria for depression (16 major depression; 8 minor depression). There was a trend towards higher K/T ratios in depressed vs. non-depressed patients (45.6+/-20.0 micromol/mmol vs. 38.5+/-15.7 micromol/mmol, F=3.778, p=.055) when controlling for age, sex and tACS. Activation of IDO is associated with the severity of depressive symptoms among patients with CAD.
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