A low 25-hydroxyvitamin D (25(OH)D) level is considered as an independent risk factor for COVID-19 severity. However, the association between vitamin D status and outcomes in COVID-19 is controversial. In the present study we investigate the association between the serum 25(OH)D level, immune response, and clinical disease course in patients with COVID-19. A total of 311 patients hospitalized with COVID-19 were enrolled. For patients with a vitamin D deficiency/insufficiency, the prevalence of severe COVID-19 was higher than in those with a normal 25(OH)D level (p < 0.001). The threshold of 25(OH)D level associated with mortality was 11.4 ng/mL (p = 0.003, ROC analysis). The frequency of CD3+CD4+ T helper (Th) cells was decreased in patients with 25(OH)D level ≤ 11.4 ng/mL, compared to healthy controls (HCs). There were no differences in the frequency of naive, central memory (CM), effector memory (EM), and terminally differentiated effector memory Th cells in patients with COVID-19 compared to HCs. The frequency of T-follicular helpers was decreased both in patients with 25(OH)D level > 11.4 ng/mL (p < 0.001) and 25(OH)D level ≤ 11.4 ng/mL (p = 0.003) compared to HCs. Patients with 25(OH)D level > 11.4 ng/mL had an increased frequency of Th2 CM (p = 0.010) and decreased Th17 CM (p < 0.001). While the frequency of Th2 EM was significantly increased, the frequency of Th17 EM was significantly decreased in both groups compared to HCs. Thus, 25(OH)D level is an independent risk factor for the disease severity and mortality in patients with COVID-19. We demonstrate that the serum 25(OH)D level ≤ 11.4 ng/mL is associated with the stimulation of Th2 and the downregulation of Th17 cell polarization of the adaptive immunity in patients with COVID-19.
Currently, heart transplantation is the key treatment for patients with end-stage heart failure. At the same time, the immunopathogenesis of chronic allograft rejection, which is a key factor in the long-term outcome, is still poorly understood, which, in turn, explains the absence of effective non-invasive methods for its detection. This review discusses up-to-date aspects of the interaction between the microbiota and immune system factors leading to inflammation and T-cell polarization, and their participation in heart transplant rejection. Special attention is paid to the role of microvesicles in immune response modulation within heart transplant rejection.
Objective. The increase in the incidence and prevalence of ulcerative colitis (UC) continues to be a worldwide trend. Both T-helpers and produced cytokines, as well as other cells of the immune system, are involved in the immunopathogenesis of UC. The aim of this study was to explore the immunological status and cytokine profile in patients with UC. Since there are significant gender differences in an immune response in inflammatory bowel disease (IBD), only men were included in this study. Patients and methods. 25 male patients with ulcerative colitis and 26 male healthy controls (HC) without IBD were enrolled in the study. T cell subsets were assessed by multicolor flow cytometry. Analysis of cytokines and chemokines in peripheral blood was performed by multiplex enzyme immunoassay. Results. The percentage of CD3+ T lymphocytes was significantly increased in UC patients compared with HC. In patients with UC, a decrease in the naive cytotoxic T lymphocytes (Tcyt) and central memory (CM) Tcyt was revealed with a significant increase in the CD3+CD8+ highly differentiated Tcyt TEMRA (terminally differentiated CD45RA-positive effector memory T-cells). CM regulatory T cells (Treg) subpopulations showed a significant negative correlation with the severity of UC, reproduced in the CD73+CD39+ Treg and CD73–CD39+ Treg subpopulations. The proportion of T follicular helper 2 cells (Tfh2) in patients with UC was significantly increased compared to НС. Analysis of the cytokine profile showed a significant increase in the concentrations of interleukins IL-5, IL-7, IL-12, IL-10, and chemokines CCL3/MIP-1α, CXCL8/IL-8, CXCL11/I-TAC, and CX3CL1/Fractalkine. Conclusion. New data were obtained on significant changes in peripheral blood T-lymphocytes and cytokine profile in male patients with UC, which turned out to be more characteristic of the Th2 response. Changes in the subpopulation composition of circulating follicular T-helpers in UC were associated with a significant increase in the percentage of Tfh2, which can switch the class of antibodies synthesized by B-cells from IgM to IgG and IgA. In addition, a significant increase in plasma concentrations of the cytokine IL-7 and the chemokine CXCL11/I-TAC was shown in patients with UC. Key words: inflammatory bowel disease, ulcerative colitis, T helper cell subsets, cytokines, chemokines
Traumatic brain injury (TBI) results in a significant inflammatory burden that increase the production of inflammatory mediators and biomarkers. The immune system plays a key role in the pathogenesis of traumatic brain injury. Neuroinflammatory mediators released from resident glia (activated microglia and astrocytes) inside the brain recruit immune cells where cytokines are small soluble proteins that confer instructions and mediate communication among immune and non-immune cells. Interleukin-6 (IL-6) is a proinflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. The purpose of the current study was to assessment of cerebrospinal fluid (CSF) interleukin-6 (IL-6) and MBP levels in patients with TBI. Samples of cerebrospinal fluid of 85 patients with TBI were examined. Concentrations IL-6 were measured via xMAP multiplexing technology. The control was the course of CSF in patients with concussion. An increased content was found in all patients with traumatic brain injury: 19.59 pg/mL in the group with mild traumatic brain injury; 103.6 pg/mL in the group with moderate traumatic brain injury; and 2225 pg/mL in the group with severe traumatic brain injury load versus 2.58 pg/mL in the control group. A direct correlation was found with the presence of basic myelin proteins in the cerebrospinal fluid, which indicates the degree of damage and neurodegeneration processes. Identification of the features of IL-6 content in patients with brain injury may indicate its important role in the course of disease. It also requires additional more detailed study, including comparison with IL-6 content in peripheral blood.
Цель исследования. Изучить влияние перорального приема цинка на функциональную активность тимоцитов при росте перевиваемой опухоли гепатомы 22а у мышей. Материалы и методы. Мыши линии C3HA, начиная с первого дня после подкожной инокуляции клеток сингенной гепатомы 22а, получали сульфат цинка с питьевой водой в концентрации 22 мкг/мл в течение трех недель. На 21 сут опухолевого роста животных выводили их эксперимента, извлекали тимусы, оценивали пролиферативную активность и апоптоз тимоцитов, а также содержание цинка в тимусе. Пролиферацию (распределение тимоцитов по стадиям клеточного цикла) изучали с помощью проточной цитометрии путем окрашивания DAPI. Для исследования апоптоза клетки окрашивали DAPI и YO-PRO. Содержание цинка в тимусе определяли с помощью атомно-абсорбционной спектрометрии. Результаты. На 21 сутки роста опухоли апоптоз тимоцитов увеличивался в 2,5 раза, а доля тимоцитов, находящихся в S фазе (фазе синтеза ДНК), снижалась в 1,8 раза. Апоптоз, главным образом, обнаруживали среди популяции двойных позитивных CD4+CD8+ тимоцитов – было отмечено увеличение в 3,2 раза по сравнению с контролем. Прием цинка нормализовал показатели пролиферативной активности (пролиферативный индекс и долю клеток в S фазе), а также снижал относительное содержание тимоцитов в состоянии апоптоза. Кроме того, прием соли цинка повышал содержание цинка в вилочковой железе. Заключение. Пероральный прием сульфата цинка вызывает торможение инволюции тимуса у мышей с гепатомой 22а и значительно улучшает показатели функциональной активности тимоцитов. У таких животных пролиферативная активность тимоцитов сохраняется на нормальном уровне, а показатели апоптоза существенно ниже, чем у животных, не получавших соль цинка. Проведенное исследование дает возможность считать пероральный прием соли цинка перспективным средством для разработки новых стратегий по восстановлению тимуса у онкологических больных.
Acute disorders of cerebral circulation are one of the leading problems of modern clinical medicine, due to their significant spread in the human population and the extremely negative impact exerted on the patient’s body. Currently available data allow us to talk about the multi-vector nature of the pathogenesis of ischemic brain damage. Within the framework of the cascade of developing pathochemical and pathophysiological processes, an essential role in the formation of ischemic stroke belongs to the inflammatory reaction occurring through the immune system’s response to cerebral tissue ischemia. One of the places of its implementation is the vessel wall located in the ischemic zone, where monocytes and neutrophils are attracted with the help of cell adhesion proteins. Complement activation plays a significant role, carried out mainly due to the C3 component or during the initialization of the mannose pathway. Activation of microglia and astrocytes plays a huge role directly in the focus of ischemia. It should be noted that in the process of activation, both microglia and astrocytes are able to acquire a pro-inflammatory or anti-inflammatory phenotype. The prevalence of the pro-inflammatory variant contributes to prolonged damage to brain tissue, while the predominance of the anti-inflammatory phenotype has a protective effect. An important role is played by a violation of the function of the blood-brain barrier, which provides an additional influx of leukocytes to the site of ischemia. In addition, individual subpopulations of T-lymphocytes penetrating through the damaged barrier also play a significant role in the organization and dynamics of the immuno-inflammatory response. The action of Th1 and Th2 cells, gamma-delta T lymphocytes, natural killer cells, as well as regulatory T lymphocytes has been most studied. The role of B-lymphocytes in the formation of a stroke focus is considered.
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