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Background: On the basis that (1) multiple interactions exist between the hormonal and immune systems, and (2) aging is accompanied by changes in thyroid hormone metabolism and responsiveness, we postulate that thyroid hormones may be involved in the observed decrease in natural killer (NK) activity in a population of apparently healthy elderly subjects. The purpose of the study is to compare NK cytotoxic activity and serum concentrations of TSH and thyroid hormones in healthy old and young people, and to assess in vitro the effects of triiodothyronine (T[sub 3] ) on NK activity. Materials and Methods: Sixteen of the 47 healthy old people (mean age 64 ± 5.2) were classified as optimally healthy, and the remainder as ‘almost healthy’ (according to the criteria of the Senieur protocol) [Ligthart et al., Mech Ageing Dev 1984;28:47–55]; the mean age of the healthy young people was 23.3 ± 2.3 years. NK cytotoxic activity of peripheral blood mononuclear cells was assessed using [sup 51] Cr release from K562 target cells. The cutoff level for defining low and high NK responses was set at a value of 20%. Serum concentrations of TSH, total thyroxine (T[sub 4] ) and total triiodothyronine (T[sub 3] ) were measured by radioimmunoassay. Results: NK activity in the ‘optimally healthy’ elderly was high (mean 41 ± 12%, SE), whereas ‘almost healthy’ subjects showed low NK activity (mean 6 ± 5%). Serum T[sub 4] and TSH levels, but not T[sub 3] concentrations were similar in both the young and old. We observed a significant correlation (r = 0.53, n = 21, p < 0.05) between the serum total T[sub 3] level and the NK activity in the elderly individuals. Under in vitro conditions exogenous T[sub 3] significantly increased NK activity in the elderly subjects who had serum T[sub 3] values at the lower end of the reference range. However, no effect of T[sub 3] on NK activity was observed in peripheral blood mononuclear cells obtained from either old or young individuals who had serum T[sub 3] levels at the midpoint of the range. Conclusion: Decreased serum concentrations of total T[sub 3] may contribute to low NK activity in the ‘almost healthy’ subgroup of the elderly.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract Background Viral and bacterial infections have been considered as a risk factor for Coronary Heart Disease (CHD). NK cells, as a first line of defense against those infections, may play a role in CHD development. Thus, the main aim of our study was to determine NK cell compartment in patients with CHD undergoing coronary artery by-pass grafting. Results Ninety three patients with CHD were included into the study; the control group consisted of 49 healthy volunteers. As compared to controls, CHD patients had lower NK cytotoxic activity. CHD group had also a decreased absolute number and percentage of total NK cells and CD3-CD56dim cytotoxic NK subset. In addition, we observed tendency toward lower percentage of the CD3-CD56bright regulatory NK subset and CD3-CD56+IFN-γ+ cells in CHD patients. Conclusion These data indicate that CHD is associated with an impairment of NK cells compartment.

The incidence of diabetes type 1, a chronic autoimmune disease, may reach the status of an epidemic in the 21st century. The highest incidence of diabetes in the world is observed in Finland. However, in the last 8 years a dynamic rise has been observed in Poland, moving the country toward an intermediate level incidence classification. Environmental factors seem to play a part in the observed increase in diabetes incidence both in Poland and in the world since, by acting on genetically predisposed ground prompt to auto-aggression, they may provoke disease occurrence. The study was carried out on a group of 511 children aged 0-15 years (255 girls and 256 boys). During the period of analysis (1998-2005) almost a two-fold increase in the diabetes incidence rate was observed (1998-10.4 vs 2005-20.4). The identification of all the factors increasing the risk of diabetes mellitus type 1 shall allow for understanding of diabetes ethiopathogenesis, and thus might create a chance for development of new prevention strategies. [ABSTRACT FROM AUTHOR]

Alternatively activated macrophages (M2) exert anti-inflammatory effects and are crucial for keeping balance between protective and destructive cell-mediated immunity in healing phase of inflammation. Two members of the interferon regulatory factors family, IRF5 and IRF4, are known to promote M1 or M2 phenotype, respectively. Our study aimed to analyse the effectiveness of the M2 differentiation process in vitro (achieved by IL-4 stimulation) and its relationship to the stage of type 1 diabetes mellitus (DM1) in juvenile patients. To identify the basic changes in M2 phenotype, we examined the expression of the surface CD206, CD14, CD86 molecules, intracellular IRF4 and IRF5 transcription factors as well as IL-10 and TNFα intracellular production. Ten newly diagnosed (ND-DM1) and ten long-standing (LS-DM1) patients were enrolled into the study. The control group consisted of six children. We observed a significantly higher number of unpolarised CD206 + CD14 + cells in the M2 cultures of DM1 subjects when compared to healthy ones. Examined cells presented common features with M1 macrophages (high levels of the CD14/CD86/IRF5 markers); however, they were weak TNFα producers in ND-DM1 patients. For the first time, we have revealed dysregulated IRF4/IRF5 axis in the analysed subpopulation derived from diabetic patients. Additionally, monocytes of ND-DM1 children were still able to differentiate into regulatory IL-10 + M2 macrophages, while this process was highly limited in LS-DM1 patients. Summarising, we suggest that the M2 polarisation process is less effective in DM1 patients than in healthy subjects and it may vary depending on the stage of disease. It can be concluded that in vitro differentiated M2 macrophages may be used in the future as inflammatory inhibitors for adoptive therapy experiments in ND-DM1 subjects.

Aim: In the currently available literature there are no works investigating the correlation between CCR5-Δ32 polymorphism and dyslipidemia in children with type 1 diabetes mellitus (T1D). Therefore, we have decided to explore the potential role played by this polymorphic locus in the incidence of dyslipidemia as an important risk factor for cardiovascular disease (CVD) in patients with T1D., Methods: A total of 380 patients with T1D were selected. Patients were divided into two groups: 180 patients with diabetic dyslipidemia and 200 controls without dyslipidemia. Characterization of CCR5-Δ32 genotypes was analyzed by polymerase chain reaction. Logistic regression model was used to examine the association between CCR5-Δ32 polymorphism and dyslipidemia., Results: When participants were analyzed according to CCR5-Δ32 polymorphism, Δ32 carriers presented higher levels of: HbA1c (p < 0.001), fasting plasma glucose (p < 0.001), LDL (p = 0.02) as well as TG (p = 0.01) and lower levels of HDL (p = 0.01) than noncarriers. Moreover, the minor allele Δ32 was more frequent in dyslipidemic subjects than controls (p < 0.001) and conferred an increased individual risk for dyslipidemia (OR = 2.327; 95% CI = 11.241-4.365; p = 0.009)., Conclusions: The findings of our study suggest that the CCR5-Δ32 polymorphism is associated with elevated plasma lipid levels and the Δ32 allele increases the risk of dyslipidemia in patients with T1D. Identification of the functional variant underlying these associations may potentially lead to the development of a novel and adjunctive approach for the treatment of dyslipidemia and CVD., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The CD83 molecule is a known marker of dendritic cell differentiation process, and its soluble form (sCD83) exerts immunosuppressive functions. In our research, we examined whether the sCD83 plasma concentration is impaired in DM1 children and if the expected changes are in line with the disturbed process of monocyte's transformation into mCD83 + monocyte-derived cells. 28 newly diagnosed (ND-DM1) and 30 long-standing (LS-DM1) patients were enrolled into our study. We revealed that the examined cells show a high mCD83 expression level in ND-DM1, which was significantly downregulated by the TNF-α stimulation. The results were in line with those from healthy controls. We also observed that monocyte differentiation process into CD83 + cells was much defective in LS-DM1 children and the mCD83 expression level seems not to be controlled by TNF-α. Moreover, the sCD83 level was significantly decreased in plasma from LS-DM1 children and it was negatively related to HbA1c levels, while no correlations were observed between TNF-α plasma concentration or disease duration. Summarizing, our results suggest that reduced sCD83 levels may correspond with a poor metabolic control in LS-DM1 patients and therapeutic administration of this molecule may indicate a new therapy approach in the chronic phase of diabetes.

Background and Aims: KLOTHO is an anti-ageing circulating hormone involved in insulin signaling, inflammation and vascular homeostasis through its protective effects on the endothelium and antioxidant actions. The common functional "KL-VS" variant of the KLOTHO gene is reproducibly associated with longevity in humans. Large number of studies have evaluated close relationship between KLOTHO protein and diabetes but the association between KL-VS variant and retinopathy in type 1 diabetes mellitus (T1D) is unknown. Therefore, in the present study we examined the association between the KL-VS polymorphism and the risk of diabetic retinopathy (DR) in patients with T1D., Methods: We examined 400 patients with T1D and 350 healthy age-matched controls. The analysis concerned KL-VS polymorphism along with the levels of serum inflammatory (CRP, TNF-α) and anti-inflammatory (IL-10) markers, pro-angiogenic (angiogenin) and anti-angiogenic interferon gamma-induced protein 10 (IP-10) factors as well as adhesion molecules (ICAM-1, ICAM-3)., Results: We did not find significant association between T1D and KL-VS alleles. However, we observed that the incidence of KL-VS genotype is lower in a group with retinopathy in comparison to diabetic patients without this complication. Moreover, we established that KL-VS carriers had the lowest levels of inflammatory markers, pro-angiogenic factors and adhesion molecules. Simultaneously, the KL-VS carriers had increased serum levels of anti-inflammatory and anti-angiogenic cytokines than holders bearing wild type genotype., Conclusions: In conclusion, the findings of our studies suggest that the functional KL-VS variant of the KLOTHO gene protects against the development of retinopathy in patients with T1D., (Copyright © 2017 Elsevier B.V. All rights reserved.)