Alterations of soluble TWEAK and CD163 concentrations in patients with chronic heart failure.

UNLABELLED: Inflammatory activation plays a pivotal role in chronic heart failure with reduced ejection fraction (HF-REF). A novel mediator from TNF family: soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) along its soluble decoy receptor CD163 (sCD163) recently has been investigated in other cardiovascular pathologies. We aimed to evaluate sTWEAK and sCD163 concentrations in HF-REF patients. The study enrolled 79 patients with stable HF-REF, EF < 35%. The control population without history of heart failure included two groups: 26 comorbidities matched patients and 27 healthy volunteers. sTWEAK and sCD163 serum concentrations were determined using ELISA kits. Univariate and multivariate analysis was performed to assess variables affecting concentration of sTWEAK and sCD163. HF-REF patients were characterized by higher sTWEAK (median 374 IQR: 321-429 vs 201 IQR: 145-412pg/ml, P=0.005), sCD163 (median 744 IQR: 570-1068 vs 584 IQR: 483-665pg/ml, P=0.03) concentrations and sTWEAK/sCD163 ratio (median 0.53 IQR: 0.32-0.7 vs 0.3 IQR: 0.22-0.37, P=0.001) comparing to healthy volunteers. Comparing to comorbidities matched controls, HF-REF patients had lower sTWEAK levels (median 374 IQR: 321-429 vs 524 IQR: 384-652pg/ml; P=0.002), while sCD163 and sTWEAK/sCD163 ratio didn't differ. Concentration of sTWEAK in HF-REF was affected by white blood cell count and aspirin intake, while sCD163 by exercise capacity, LV diastolic volume, CRP and presence of arterial hypertension. CONCLUSIONS: HF-REF patients present increased sTWEAK and sCD163 levels as well as sTWEAK/sCD163 ratio when compared to healthy subjects, however CHF itself appears to be associated with down-regulation of sTWEAK.

Vitamin D3 Treatment Decreases Frequencies of CD16-Positive and TNF-α-Secreting Monocytes in Asthmatic Patients.

BACKGROUND: Previously, we demonstrated that glucocorticoid (GC) treatment of asthmatic patients resulted in decreasing frequencies of monocyte subsets expressing CD16 and capable of releasing TNF-α. Here, we wished to analyze whether the active form of vitamin D, i.e. vitamin D3, referred to as 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can exert GC-like proapoptotic effects on CD16-positive monocytes and thus decrease the proinflammatory potential of these cells. Finally, we set out to investigate whether the addition of 1,25-(OH)2D3 would facilitate the use of lower doses of GC without decreasing their anti-inflammatory properties. METHODS: Peripheral blood mononuclear cells collected from healthy individuals and asthmatic patients were cultured with 1,25-(OH)2D3 and/or varying doses of GC in the presence or absence of caspase inhibition. The cells were either directly stained for extracellular markers or prestimulated with lipopolysaccharide for the assessment of intracellular cytokine production and then analyzed by flow cytometry. RESULTS: We found that 1,25-(OH)2D3 alone (and in combination with GC) decreased the frequency of CD14++CD16+ and CD14+CD16++ monocytes from asthmatic patients and significantly diminished TNF-α production by the monocytes. With regard to the CD14+CD16++ subset, the monocyte-depleting effects of 1,25-(OH)2D3 were abrogated in the presence of pan-caspase inhibitor, suggesting a proapoptotic mechanism of 1,25-(OH)2D3 action. Interestingly, we found that a combined treatment of 1,25-(OH)2D3 and GC allowed for a 5-fold reduction of the GC dose while maintaining their anti-inflammatory effects. CONCLUSIONS: This study has revealed novel immunomodulatory properties of 1,25-(OH)2D3 directed against monocyte subsets capable of TNF-α production. In addition, our data suggest that the introduction of 1,25-(OH)2D3 to anti-inflammatory therapy would possibly allow for the use of lower doses of GC.

Differences in Monocyte Subsets and Monocyte-Platelet Aggregates in Acute Myocardial Infarction-PreliminaryResults.

BACKGROUND: Monocyte-platelet interaction may favor the development of a proatherogenic monocyte phenotype. It is still uncertain which of the 3 monocyte subpopulations interact with platelets to form monocyte-platelet aggregates (MPAs) in acute myocardial infarctions. The aim of our study was to evaluate the monocyte subsets, the percentage of MPAs and the involvement of monocyte subsets in MPA formation among patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), and compared to patients with stable angina (SA). METHODS: Monocyte subsets and MPAs formation were measured in blood collected in 3.2% sodium citrate tubes by means of flow cytometry. RESULTS: Classical, intermediate and nonclassical monocyte percentages were statistically different when comparing patients with STEMI and NSTEMI. Moreover, classical and intermediate monocytes were statistically different when comparing the STEMI and SA group; however, only the classical monocyte subset was found to be higher in the acute myocardial infarction group compared to the SA group. The percentage of MPAs was significantly higher in STEMI (50.1%) compared to NSTEMI (22.9%). We found no differences in the involvement of monocyte subsets in MPA formation between patients with STEMI and NSTEMI and in comparison with the SA group. CONCLUSIONS: These findings suggest that the increase in circulating levels of classical monocytes in patients with STEMI as compared to NSTEMI reflects the severity of the acute event. The increased percentage of MPAs may favor the development of STEMI compared to NSTEMI.

Effect of Periodic Granulocyte Colony-Stimulating Factor Administration on Endothelial Progenitor Cells and Different Monocyte Subsets in Pediatric Patients with Muscular Dystrophies.

Muscular dystrophies (MD) are heterogeneous group of diseases characterized by progressive muscle dysfunction. There is a large body of evidence indicating that angiogenesis is impaired in muscles of MD patients. Therefore, induction of dystrophic muscle revascularization should become a novel approach aimed at diminishing the extent of myocyte damage. Recently, we and others demonstrated that administration of granulocyte colony-stimulating factor (G-CSF) resulted in clinical improvement of patients with neuromuscular disorders. To date, however, the exact mechanisms underlying these beneficial effects of G-CSF have not been fully understood. Here we used flow cytometry to quantitate numbers of CD34+ cells, endothelial progenitor cells, and different monocyte subsets in peripheral blood of pediatric MD patients treated with repetitive courses of G-CSF administration. We showed that repetitive cycles of G-CSF administration induced efficient mobilization of above-mentioned cells including cells with proangiogenic potential. These findings contribute to better understanding the beneficial clinical effects of G-CSF in pediatric MD patients.

Circulating classical CD14++CD16- monocytes predict shorter time to initial treatment in chronic lymphocytic leukemia patients: Differential effects of immune chemotherapy on monocyte-related membrane and soluble forms of CD163.

Three main monocyte subsets: classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++, differentially regulate tumor growth and survival. Thereby, in the present study we aimed to determine the role of distinct monocyte subsets in the prognostication of chronic lymphocytic leukemia (CLL). Moreover, we set out to analyze the effects of standard immune chemotherapy on different monocyte subsets and levels of membrane-associated and soluble forms of CD163, a monocyte/macrophage-related immunomodulatory protein. We demonstrated that the number of peripheral blood classical CD14++CD16- monocytes assessed at the time of diagnosis was negatively correlated with lymphocytosis and was decreased in the CLL patients who required immediate treatment as opposed to patients who qualified to 'watch and wait' strategy. Notably, lower baseline levels of classical CD14++CD16- monocytes in CLL patients who were qualified for 'watch and wait' therapy were associated with shorter time to initial treatment. Notably, therapy with rituximab, cyclophosphamide and fludarabine resulted in a significant reduction in the number of non-classical CD14+CD16++ monocytes and soluble form of CD163 but upregulation of membrane-associated monocyte CD163. Our data indicate that distinct monocyte subsets and two forms of CD163 are differentially modulated by both CLL and immune chemotherapy. Moreover, we proposed that quantification of classical monocytes at the time of diagnosis contributes to better prognostication of CLL patients.