Peripheral blood lymphocyte subpopulations in patients with bipolar disorder type II.

We investigated the phenotype of peripheral blood lymphocytes of patients with bipolar disorder type II in different phases of the disease in order to check whether there are specific changes in the immune parameters. Lymphocytes subpopulations were analyzed ex vivo with flow cytometry in patients in euthymic, depression or hypomanic phase of the disease and compared with healthy controls. All BD patients were characterized by lower percentage of CD3+CD4+ and CD3+CD8+ cells compared with healthy people. But only patients in depression and remission had higher percentage of B cells (CD19+ cells) compared with healthy people. The percentage of CD4+CD25+ and CD8+CD25+ cells was decreased in patients in hypomanic phase compared with healthy control. Patients in remission were characterized by increased concentrations of IL-6 and IL-10 and decreased level of TNF in blood serum. Significant correlations between immunologic parameters and the results of Hamilton or Young scale have also been found. Our results demonstrate that there are significant differences in lymphocyte subpopulations which depend on the phase of the disease the patient is currently in.

The influence of a single hemodialysis procedure on human T lymphocytes.

At the moment it is unknown to what extent the impaired function of T lymphocytes in ESRD patients depends on uremia, and to what extent on hemodialysis (HD) procedure. Therefore, the purpose of the study was to evaluate percentages of T lymphocyte subpopulations ex vivo, plasma concentrations of IL12p70, TNF, IL-10, IL-6, IL-1ß, IL-8 cytokines and selected proliferation parameters of in vitro activated T lymphocytes in HD patients before and after single HD procedure using flow cytometry. We demonstrated that the percentage of CD8+ cells ex vivo was decreased while the CD4+/CD8+ ratio was increased after HD procedure. Also, there was significant decrease in the percentage of CD8+HLA-DR+, CD8+CD69+ and CD8+CD95+ cells after HD. At the same time, an increase in the percentage of CD4+CD95+ cells was observed after HD. From all analyzed cytokines, only the concentration of IL-8 was significantly decreased after HD procedure. A single HD session enhanced proliferation capacity of CD4+ cells but not CD8+ cells in vitro by increasing number of cell divisions and percentage of dividing cells. Our results show that a single hemodialysis can have immunomodulatory effect on HD patients and may contribute to the state of immune deficiency observed in patients with ESRD.

The Level of Cytokines in the Vitreous Body of Severe Proliferative Diabetic Retinopathy Patients Undergoing Posterior Vitrectomy.

OBJECTIVE: The objective of the study was to compare cytokine levels in the vitreous body of patients with proliferative diabetic retinopathy (PDR) undergoing posterior vitrectomy. PATIENTS AND METHODS: The study included 39 patients (39 eyes) undergoing pars plana vitrectomy (PPV). Patients were divided into three groups: patients with proliferative diabetic retinopathy (PDR) without aflibercept injection prior to the surgery, PDR patients administered aflibercept injection prior to the surgery, and patients without diabetes mellitus (control group). All patients underwent a comprehensive eye examination one day before and 3 weeks after the surgery, including measurements of: best-corrected visual acuity (BVCA) and intraocular pressure (IOP), slit-lamp examination and spectral domain optical coherence tomography (SOCT). Concentrations of cytokines: IL-6, IL-8, IL-12p70, TNF, IL-10, IL-1ß were measured in the vitreous body of patients with BD™ Cytometric Bead Array (CBA) Human Inflammatory Cytokines Kit. RESULTS: PDR patients who received pretreatment with aflibercept injection showed significantly lower concentrations of IL-12p70, TNF, IL-10 and IL-1ß in the vitreous body compared to the control group. Meanwhile, patients without prior aflibercept injection had a significantly higher concentration of IL-8. There was also a significant positive correlation between IOP before PPV and IL-8 concentration in both PDR patients' groups. CONCLUSION: Findings of our study suggest an important role of IL-8 in the development of severe PDR. Aflibercept administration on the day before elective vitrectomy facilitated the surgery.

Proliferation and apoptosis of T lymphocytes in patients with bipolar disorder.

The aim of the study was to evaluate proliferation capacity and susceptibility to apoptosis of T lymphocytes of patients with bipolar disorder (BD) and to investigate in vitro influence of two standard mood stabilizers: lithium and valproic acid on these parameters using flow cytometry. Our results show that T lymphocytes of BD patients, especially those treated with lithium, have reduced proliferation capacity compared to healthy people. In vitro studies showed that valproic acid reduces the number of cell divisions and percentages of proliferating cells regardless of health status but mainly in very high dose, while lithium has no significant influence on proliferation capacity of patients' T lymphocytes. Lymphocytes of BD patients are also more prone to apoptosis compared with healthy individuals which is related to high expression of Bax, a pro-apoptotic protein. In vitro lithium protected patients' lymphocytes from apoptosis proportionally to dose used. Valproic acid protected lymphocytes of patients from apoptosis mainly in therapeutic concentration. Our results show that mood stabilizers used to prevent relapses of the disease have anti-apoptotic effect on T lymphocytes of BD patients but they are not able to improve their proliferation capacity.

Homeostatic 'bystander' proliferation of human peripheral blood B cells in response to polyclonal T-cell stimulation in vitro.

The mechanisms of maintenance of adequate numbers of B lymphocytes and of protective levels of immunoglobulins in the absence of antigenic (re)stimulation remain not fully understood. Meanwhile, our results presented here show that both peripheral blood naive and memory B cells can be activated strongly and non-specifically (in a mitogen-like fashion) in 5-day in vitro cultures of anti-CD3- or concanavalin A (Con A)-stimulated peripheral blood mononuclear cells of healthy people. This polyclonal, bystander activation of the B cells includes multiple divisions of most of them (assessed here by the flow cytometric technique of dividing cell tracking) and significant antibody [immunoglobulin M (IgM) and IgG] secretion. Observed proliferation of the CD19(+) B cells depends on contact with stimulated T helper (Th) cells (via CD40-CD40L interaction) and on the response of B cells to secreted interleukins IL-5, IL-10 and IL-4, and is correlated with the levels of these Th-derived molecules, while it does not involve the ligation of the BCR/CD19 complex. We suggest that the effect might reflect the situation occurring in vivo as the homeostatic proliferation of otherwise non-stimulated, peripheral B lymphocytes, providing an always ready pool for efficient antibody production to any new (or cognate) antigen challenge.