Decreased natural killer cell activity as a potential predictor of hypertensive incidence.

Introduction: Blood pressure is closely linked with immune function. This study examined the association between natural killer (NK) cell activity (NKA) and blood pressure and the development of hypertension according to NKA levels. Methods: This study enrolled 1543 adults who underwent NKA measurement and serial health check-ups at a medical center in Korea. NKA was estimated as the concentration of IFN-γ in the incubated whole blood containing a patented stimulatory cytokine. The participants were categorized into quartiles according to their NKA levels. Participants without hypertension were followed up, and the development of hypertension was compared according to the quartiles. Results: The prevalence of hypertension was not different among the NKA quartiles, whereas blood pressures significantly decreased, followed by an increment of quartiles (systolic blood pressure of 119.0 in Q1 and 117.0 in Q4, P-trend = 0.018). Over a mean follow-up period of 2.13 years, hypertension developed in 156 of 1170 individuals without baseline hypertension. The hazard ratio of Q4 compared with Q1 was 0.625 (95% CI: 0.397-0.983; p = 0.042). Conclusion: In conclusion, our findings indicate a correlation between lower NKA and higher blood pressure and the development of incident hypertension. This may suggest a potential protective role of NK cells against endothelial dysfunction. Further research is necessary to elucidate the specific relationship between immune functions and endothelial function.

Low Muscle and High Fat Percentages Are Associated with Low Natural Killer Cell Activity: A Cross-Sectional Study.

This study aimed to investigate whether body fat and muscle percentages are associated with natural killer cell activity (NKA). This was a cross-sectional study, conducted on 8058 subjects in a medical center in Korea. The association between the muscle and fat percentage tertiles and a low NKA, defined as an interferon-gamma level lower than 500 pg/mL, was assessed. In both men and women, the muscle mass and muscle percentage were significantly low in participants with a low NKA, whereas the fat percentage, white blood cell count, and C-reactive protein (CRP) level were significantly high in those with a low NKA. Compared with the lowest muscle percentage tertile as a reference, the fully adjusted odd ratios (ORs) (95% confidence intervals (CIs)) for a low NKA were significantly lower in T2 (OR: 0.69; 95% CI: 0.55-0.86) and T3 (OR: 0.74; 95% CI: 0.57-0.95) of men, and T3 (OR: 0.76; 95% CI: 0.59-0.99) of women. Compared with the lowest fat percentage tertile as a reference, the fully adjusted OR was significantly higher in T3 of men (OR: 1.31; 95% CI: 1.01-1.69). A high muscle percentage was significantly inversely associated with a low NKA in men and women, whereas a high fat percentage was significantly associated with a low NKA in men.

Relationship between Serum Cortisol, Dehydroepiandrosterone Sulfate (DHEAS) Levels, and Natural Killer Cell Activity: A Cross-Sectional Study.

The adrenal steroid hormones, cortisol and dehydroepiandrosterone sulfate (DHEAS), are associated with the immune system in opposite actions. This study aimed to investigate the relationship between cortisol and DHEAS serum concentrations, their ratio (CDR), and natural killer cell activity (NKA). This cross-sectional study included 2275 subjects without current infection or inflammation in the final analyses. NKA was estimated by measuring the amount of interferon-gamma (IFN-γ) released by activated natural killer cells; low NKA was defined as IFN-γ level < 500 pg/mL. Cortisol, DHEAS levels, and CDRs were categorized by quartiles in men, premenopausal women, and postmenopausal women. Compared with the lowest quartile as reference, the adjusted odd ratios (ORs) and 95% confidence intervals (CIs) for low NKA of the highest cortisol and CDR group were 1.66 (1.09-2.51) and 1.68 (1.11-2.55) in men, 1.58 (1.07-2.33) and 2.33 (1.58-3.46) in premenopausal women, and 2.23 (1.28-3.87) and 1.85 (1.07-3.21) in postmenopausal women. Only in premenopausal women, the highest DHEAS group showed significantly lower risk of low NKA (OR: 0.51, 95% CI: 0.35-0.76). HPA axis activation indicated as high cortisol level, CDR was significantly associated with low NKA, while high DHEAS levels were inversely associated with low NKA in premenopausal women.

A Case-Control Study on the Changes in Natural Killer Cell Activity following Administration of Polyvalent Mechanical Bacterial Lysate in Korean Adults with Recurrent Respiratory Tract Infection.

Polyvalent mechanical bacterial lysate (PMBL) is used for the treatment and prevention of recurrent respiratory tract infections. Although PMBL is an immunostimulant, it remains unknown whether treatment with PMBL influences natural killer cell activity (NKA). Hence, this case-control study compared the changes in IFN-γ levels (surrogate index for NKA) following PMBL treatment or time passing between the PMBL-treated group and controls. The treatment group included adults who had a PMBL prescription for three months against recurrent respiratory tract infection from an outpatient clinic, while the control group had healthy adults visiting the health promotion center for periodic health check-ups. The control group (N = 506) showed no change in IFN-γ levels, while the treatment group (N = 301) showed a significant increase in mean from 462.8 to 749.3 pg/mL after PMBL treatment. In the subgroup with IFN-γ <500 pg/mL, IFN-γ levels significantly increased in both groups. However, the change in the treatment group (287 ± 822 pg/mL) was greater than that in the control group (58 ± 809 pg/mL), and the interaction between the visit and case/control was significant (p = 0.030) in a generalized estimating equation model. In conclusion, NKA increased in the subjects with recurrent respiratory tract infections with PMBL treatment.

Characteristics of Urine Organic Acid Metabolites in Nonalcoholic Fatty Liver Disease Assessed Using Magnetic Resonance Imaging with Elastography in Korean Adults.

The liver is an essential organ that manufactures energy through various metabolic pathways; thus, exploring the intermediate metabolites in nonalcoholic fatty liver disease (NAFLD) may help discover novel parameters in hepatic steatosis or fibrosis. The present study aimed to investigate the traits of urine organic acid metabolites in participants with hepatic steatosis and fibrosis in nonalcoholic Korean adults. Hepatic steatosis and fibrosis, in 68 men and 65 women, were evaluated using quantification by proton density fat fraction with magnetic resonance (MR) imaging and MR elastography, respectively. Urine metabolites were obtained using a high-performance liquid chromatography-mass spectrometry analysis. The candidate metabolites were included in the logistic regression models for hepatic steatosis and fibrosis. The association between high p-hydroxyphenyllactate levels and hepatic steatosis was not independent of body mass index and Homeostatic Model Assessment-insulin resistance. High ethylmalonate, ß-hydroxybutyrate, and sulfate levels were significantly related to a low probability of hepatic fibrosis, independent of covariates. In conclusion, urine metabolites were not related to hepatic steatosis independent of obesity and insulin resistance, while several metabolites were specifically associated with hepatic fibrosis. Further study is required to verify the diagnostic value of the metabolites in a population with wide-spectrum NAFLD.

Cross-Sectional and Time-Dependent Analyses on Inflammatory Markers following Natural Killer Cell Activity.

The function of natural killer (NK) cells in inflammation has not been explored enough in large-scale population studies. The cross-sectional and time-dependent relationship between NK cell activity (NKA) and inflammatory markers was examined. METHODS: A total of 7031 subjects were involved in the cross-sectional analyses. Non-linear relationship between NKA and inflammatory indices was analyzed using generalized additive models. The time-dependent changes were analyzed in 1005 subjects with repeated measurement in 3-6 months. The changes in inflammatory markers were analyzed based on the changes in NKA. RESULTS: As NKA reduces to a very low level, the white blood cell (WBC) and neutrophil counts increase sharply, and the lymphocyte count exhibits a slow decline. With increasing NKA larger than about 500 pg/mL, WBC and neutrophil-lymphocyte ratio (NLR) reduces in a mild slope. Among the subjects with repeated measurements, the follow-up NKA was increased with advancing baseline NKA levels. The subjects with a reduction in NKA indicated increment in WBC count, neutrophil count, and NLR, and decrease in lymphocyte count. CONCLUSIONS: Very low levels of NKA suggest a high inflammatory immune response. The changes in NKA may interact with the balance between neutrophils and lymphocytes.

Urine organic acids may be useful biomarkers for metabolic syndrome and its components in Korean adults.

OBJECTIVES: Although metabolic syndrome (MetS) and its components are defined clinically, those with MetS may have various derangements in metabolic pathways. Thus, this study aimed to evaluate the traits of urine organic acid metabolites indicating the metabolic intermediates of the pathways in the subjects with MetS. METHODS: This cross-sectional study included 246 men and 283 women in a hospital health check-up setting. Urine organic acid metabolites were assayed via high-performance liquid chromatography-mass spectrometry analyses. A high level of each metabolite was defined as the fifth quintile of the distribution. RESULTS: The subjects with MetS had high levels of pyruvate, α-ketoglutarate, α-ketoisovalerate, α-ketoisocaproate, formiminoglutamate, and quinolinate (odds ratios from 1.915 to 2.809 in logistic models adjusted for age and sex). Among the metabolites, pyruvate, formiminoglutamate, and quinolinate were not independent of homeostatic model assessment of insulin resistance (HOMA2-IR). Several metabolites were associated with one or more components of MetS and HOMA2-IR. CONCLUSIONS: Urine organic acid metabolites in MetS are characterized in altered carbohydrate and amino acid metabolism. MetS shared some traits in insulin resistance. These findings may promote the understanding of the pathophysiology of MetS.

Elevated levels of urine isocitrate, hydroxymethylglutarate, and formiminoglutamate are associated with arterial stiffness in Korean adults.

Recent evidence suggests that cellular perturbations play an important role in the pathogenesis of cardiovascular diseases. Therefore, we analyzed the association between the levels of urinary metabolites and arterial stiffness. Our cross-sectional study included 330 Korean men and women. The brachial-ankle pulse wave velocity was measured as a marker of arterial stiffness. Urinary metabolites were evaluated using a high-performance liquid chromatograph-mass spectrometer. The brachial-ankle pulse wave velocity was found to be positively correlated with L-lactate, citrate, isocitrate, succinate, malate, hydroxymethylglutarate, α-ketoisovalerate, α-keto-ß-methylvalerate, methylmalonate, and formiminoglutamate among men. Whereas, among women, the brachial-ankle pulse wave velocity was positively correlated with cis-aconitate, isocitrate, hydroxymethylglutarate, and formiminoglutamate. In the multivariable regression models adjusted for conventional cardiovascular risk factors, three metabolite concentrations (urine isocitrate, hydroxymethylglutarate, and formiminoglutamate) were independently and positively associated with brachial-ankle pulse wave velocity. Increased urine isocitrate, hydroxymethylglutarate, and formiminoglutamate concentrations were associated with brachial-ankle pulse wave velocity and independent of conventional cardiovascular risk factors. Our findings suggest that metabolic disturbances in cells may be related to arterial stiffness.