RESUMEN
Some changes in lipid metabolism and immune status occurring at aging are accompanied with development of inflammatory metabolic disorders and age-associated pathologies. It is well-known that permanent stimulation of immune responses may lead to hyperlipidemia that, in its turn, may evoke immune disturbances and affect the auto-inflammation processes. It seems important to explore a mutual relationship between lipid metabolites and immunology markers in order to better manage the age-associated diseases. In Georgian population the study on associations between the lipid metabolism and the immunological parameters might be especially interesting due the specific geo-climate environment and dietary peculiarities of the country. Study involved 250 healthy volunteers at the age of 18-80 years that were tested on the lymphocyte sub-populations (CD3+CD4+, CD3+CD8+, CD4+CD8+, CD4+CD25+FoxP3+) in peripheral blood, as well as on the levels of lipids (Low-and High density lipoproteins, triglycerides and total cholesterol levels. The study revealed statistically significant differences between the under-60 and above-60 age groups by the level of lipids (low density lipoproteins and total cholesterol) and of CD4+CD25+FoxP3+ cell counts in the healthy population of Georgia. Meanwhile, the lipid fractions (low density lipoproteins, triglycerides and total cholesterol) showed statistically reliable positive correlation with CD4+CD8+ cell but negative correlation with CD4+CD25+FoxP3+cell counts.
Asunto(s)
Envejecimiento/sangre , Citocinas/sangre , Inflamación/sangre , Lípidos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Colesterol/sangre , Femenino , Voluntarios Sanos , Humanos , Inflamación/patología , Lipoproteínas/sangre , Lipoproteínas/fisiología , Masculino , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
Type 1 diabetes (T1D) is an inflammatory disease of the pancreatic islet, in which insulin-producing ß-cells are preferentially destroyed to varying degrees by the concerted action of autoreactive T-cells and monocytic cells. Th1-type cytokines (IL-2 and IFN-γ) correlate with T1D, whereas Th2 (IL-4 and IL-10), Th3 (TGF-ß), and T regulatory cell-type cytokines (IL-10 and TGF-ß) correlate with protection from T1D. An altered balance between the proinflammatory and regulatory T-cell responses, in which T regulatory cells lose the battle, leads to T1D. The aim of current study was to determine the role of CD4+CD25+ regulatory T cells and cytokines: IFN-γ, IL-6, TNF-α, IL-10, IL-4, IL-17 in pathogenesis of T1D.The study was carried out on 71 patients suffering from T1D at the department of endocrinology, Tbilisi State Medical University and Diabetic Children Association. The circulating levels of (IFN-γ, IL-6, TNF-α, IL-10, IL-4, IL-17) were determined by ELISA according manufactures' protocol (R&D Systems Inc., USA). Tregs - CD4+CD25+ frequency was determined on cytofluorometer (BD FACSCalibur flow cytometer, USA). Statistical analysis was performed by using STATISTICA 8.0 for PC (Statsoft Inc., Minneapolis, USA) and Mann-Whitney U-test. Our study revealed significant decrease of IL-6, TNF-α, IL-10 and IL-4 plasma levels (1.197-, 1.188-, 1.504- and 1.840-times respectively) and increase of IL-17 plasma level (2.311-times) on the background of almost unchanged frequency of Tregs in patients with type 1 diabetes. In T1D patients CD4+CD25+ Tregs frequency did not correlate with diabetes duration and positivly correlated with age and IL-4. We supposed that decreased level of IL-4 and IL-10 reflects inhibited functional activity of these cells. We suggested that shifted balance of Th17/Tregs towards inflammatory IL-17 producing cells and decreased levels of suppressive cytokines IL-4 and IL-10 play crucial role in T1D. Future studies are needed to clarify changes in which subsets of heterogenous population of regulatory cells are associated with diabetes duration and how the therapy affects their frequency and function.