Mechanisms of immune regulation and transplantation immunity in corneal transplants

At the present time, corneal transplantation (keratoplasty) is one of the most frequent modes of solid tissue transplants in the world. Unlike other kinds of transplants, corneal grafting is often performed without tissue typing and systemic immunosuppression.High frequency of transparent corneal engraftment (up to 90% of cases) in the absence of risk factors is due to special immunoprivileged area in the anterior eye segment (functionally, a structural aggregation of the cornea and anterior chamber, AC) accomplished by local and systemic immunoregulatory mechanisms, i.e., phenomenon of immune deviation associated with anterior chamber of the eye (ACAID), components of the internal liquid medium, a watery moisture with immunosuppressive properties, e.g., IL-1ra, TSP-1,TGF-β2, regulatory complement proteins, α-MSH (alpha-melanocyte stimulating hormone), VIP (vasoactive intestinal peptide), indolamine 2,3-dioxygenase (IDO), calcitonin-gene-bound peptide (CGRP), somatostatin, etc.In addition to ACAID and liquid AC components, a contribution to the maintenance of immune privilege which is extremely important for a successful outcome of keratoplasty, is provided by other mechanisms, in particular, immunologically active membrane-associated molecules of corneal endothelium, i.e., PDL-1 (Programmed death ligand 1), and sVEGFR-1, sVEGFR-2, sVEGFR-3 involved in maintaining avascularity of the corneal tissue. Disturbances of the immune privilege of the cornea promotes activation of immune recognition with switching the effector mechanisms of transplantation immunity, thus leading to subsequent development of the tissue incompatibility reaction and clouding of transplanted cornea. Graft rejection can be localized in any of the corneal cell layers, including epithelium, stroma, and endothelium. Endothelial rejection causes the most severe affection of visual functions, due to the inability of local endothelial recovery, and water accumulation due to the endothelial dysfunction.Graft rejection is clinically characterized by edema and the presence of inflammatory cells, either circulating in the anterior chamber, or forming precipitates on the graft endothelial cells.A number of factors are associated with an increased risk of corneal graft rejection, including the degree of inflammation and/or vascularization of the transplant bed i.e., location of the donor cornea, repeated keratoplasty, allosensitization due to other cellular transplants, including bone marrow, blood transfusions, pregnancy, etc., as well as allergic and systemic diseases.This review article considers and systematizes the data from the literature concerning studies of the factors determining the immune privileged state of cornea, and the ACAID phenomenon, their role in development of allotolerance in corneal transplantation, highlights the main conditions required for triggering the tissue incompatibility reactions, discusses the mechanisms of allogeneic recognition and effector stage of the immune response, destruction of corneal allografts

Local and systemic production of 45 cytokines in complicated proliferative diabetic retinopaty

Diabetic retinopathy (DR) is multifactorial by its origin, involving many cytokines and growth factors. Studies of cytokine levels in biological fluids seem to be relevant for an in-depth understanding of the disease pathogenesis. The purpose of the work was a comparative analysis of 45 cytokines at systemic (blood serum (BS)) and local (vitreous humor (VH)) levels in the patients with complicated proliferative DR, showing various features of the clinical pattern. The content of cytokines was tested in 53 samples of BS and 32 samples of VH in 53 patients with type 1 and type 2 diabetes mellitus with severe proliferative DR. We used the multiplex analysis technique by means of xMAP platform and Luminex xPONENT 3.1 program using 45-plex sets (Procarta Plex «eBioscience», Austria). 25 cytokines were detected at significant amounts in BS test samples, and 27 cytokines were revealed in VH specimens. Sensitivity limits of the test system allowed to find significantly higher levels of 7 cytokines (IL-6, IL-8, IP-10, MCP-1, HGF, LIF and VEGF-A) in VH samples, than in the BS, thus indicating to their local intraocular production. Correlations between the contents of VEGF-A growth factor and amounts of cytokines, including those involved in inflammatory reactions, are shown in VH, thus presuming the interrelation of pathogenetic components, i.e., inflammation and neoangiogenesis. The features of intraocular cytokine content were determined for various manifestations of diabetic ocular changes. Hemophthalmus has been shown to be associated with increased IL-8 and IP-10; iris rubeosis, with increase in LIF; proliferative DR activity was associated with higher MCP-1 levels, and extremely severe changes were related to increase in IL-6 and EGF. Testing of cytokines in biological fluids is informative when studying the mechanisms of inflammation, neoangiogenesis, and protective responses in pathogenesis of diabetic retinopathy

Proven and less studied hematopoietic and vasoactive growth factors in retinal capillary hemangioma

Pathogenesis of retinal capillary hemangioma has not been sufficiently studied at the present time. Therefore, the study of cytokine levels in biological fluids seems to be very relevant in order to increase knowledge about the mechanisms of the disease development and searching for targeted therapies. The content of hematopoietic and vasoactive growth factors in blood serum, lacrimal fluid, and vitreous body was studied in patients with retinal capillary hemangioma. A total of 26 patients with retinal angiomatosis were examined. The samples of blood serum (n = 23) and lacrimal fluid (n = 10) from practically healthy people aged 22 to 46 (27.4±1.4 years) were used as a control. To perform comparative assessment of cytokine concentrations in the vitreous body of patients with retinal capillary hemangioma, were used samples of the vitreous body from 6 patients (average age 33±4.7 years; from 21 to 49 years) with rhegmatogenous retinal detachment. To measure the cytokine concentrations, we applied multiplex analysis technique using the xMAP platform with LuminexxPONENT 3.1 program and ProcartaPlex sets (eBioscience, Austria). A detailed characteristic of vasoactive factors in capillary retinal hemangioma was obtained as a result of this work. Some disorders in chemokine regulation were identified. There was a significant increase in serum concentrations of three vasoactive factors, i.e., PDGF-BB, HGF, and PIGF-1, with a decrease in chemokines (MCP-1, MIP-1α, and MIP-1β). The frequencies of PIGF-1 and MIP-1α detection also significantly differed from the control group. SCF was significantly more often determined in patients with retinal angiomatosis only at the systemic level. Correlations between PDGF-BB and PIGF-1, as well as PIGF-1 and MIP-1β were shown. A significant increase in VEGF-A, HGF, VEGF-D, as well as MCP-1 concentrations was shown in the lacrimal fluid. The inversion of PDGF-BB concentrations in serum and lacrimal fluid was noted. Analysis of intraocular cytokine levels revealed a significant increase in VEGF-A and HGF concentrations, with marked decrease in MIP-1α and MIP-1β. PDGF-BB in 100% of cases was determined only in vitreous body of patients with retinal angiomatosis. With respect to the revealed characteristic shifts of HGF/SF intraocular production in retinal capillary hemangioma, it seems relevant to search ways for its inhibition, thus providing potential basis for a new therapeutic strategy in treatment of retinal angiomatosis

Screening of cytokines in blood serum and lacrimal liquid in wet and atrophic forms of age-related macular degeneration

Cytokines play an integral role in pathogenesis of age-related macular degeneration (AMD). Of particular interest are the late stages of this disease, which causes progressive visual impairment. Therapy-induced effects of post-treatment cytokine concentrations also need to be studied, both at long and short observation terms. These studies are of vital importance if the atrophy occurs during antiangiogenic therapy. Our purpose was to study an array of 45 cytokines, in blood serum (BS) and lacrimal liquid (LL) of the patients with wet and atrophic AMD.The study included 70 people (85 eyes) with stage 3-4 AMD according to AREDS. Depending on the form of AMD, 3 groups were discerned: I group (n = 24) included the patients with “geographic atrophy”; II group (n = 22), consisted of the patients with macular atrophy treated with antiangiogenic therapy of wet AMD; III group (n = 24), comprised the patients with a wet AMD who did not previously receive the treatment. Control group consisted of healthy volunteers (n = 25). All the groups were comparable for age and gender. The patients underwent a comprehensive ophthalmological examination to make a diagnosis. A multiplex study of the local (in the BS) and systemic (in the LL) cytokine status was carried out on a MAGPIX device (platform хMAP, Luminex Corporation, USA) in the Luminexx PONENT 3.1 software, using Procarta Plex kits (eBioscience, Austria). We determined 45 cytokines causing various biological effects, i.e., IL-1á, IL-1â, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IL-31, IFNá, IFNã, IL-8/CXCL8, IP-10/CXCL10, SDF-1á/CXCL12, MCP-1/CCL2, MIP-1á/CCL3, MIP-1â/ CCL4, RANTES/CCL5, Eotaxin/CCL11, TNFá, TNFâ, GM-CSF, VEGF-A, VEGF-D, FGF-2, EGF, PDGF-BB, HGF, SCF, GRO-á, NGF-â, BDNF, LIF, PIGF-1.Screening of a wide range of cytokines showing various biological effects was carried out in BS and LL of patients with atrophic and wet forms of AMD. It has been shown that the late stages of the disease are associated with local and systemic changes of pro / anti-inflammatory mediators (IL-1â, IL-1ra, IL-18, LIF), chemoattractant cytokines (IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, MIP-1á/CCL3, MIP-1â/ CCL4, RANTES/CCL5, Eotaxin/CCL11), hematopoietic regulators (IL-7), and growth factors with known angiogenic activity (EGF, HGF, PDGF-BB, VEGF-A). Altered concentrations of numerous chemokines, e.g., IP-10/CXCL10, SDF-1á/CXCL12, MIP-1á/CCL3, MIP-1â/CCL4, RANTES/CCL5 and Eotaxin/CCL11 (p < 0.05) in BS of the patients with atrophic and wet AMD may be of interest for the search of biomarkers associated with various clinical phenotypes of the disease and may be also helpful for development of new therapeutic strategies

Investigation of local expression of NLRP3 inflammasome complex genes in modeling retinal degeneration <i>in vivo</i>

Neurodegenerative ophthalmopathology is one of the main causes of irreversible blindness and disability in the world. In the pathogenesis of diseases of this group, more and more attention has recently been paid to the role of local inflammation caused by the activation of innate immunity and the mechanisms of its genetic regulation. In recent years, works have appeared in the field of experimental ophthalmology that have demonstrated the possibility of NLRP1, NLRP3 inflammasome complexes assembling when exposed to hyperglycemia, oxygen deprivation of retinal cells, as well as modeling compressive stress similar to that in glaucoma [15]. However, the mechanism of inflammasome involvement in the development of neurodegenerative eye diseases remains unclear. The aim of the study was to investigate the local expression of genes encoding proteins of the NLRP3 inflammasome complex (NLRP3, CASP-1) in an experimental model of retinal degeneration in rabbits. The studies were performed on samples of tissue complex (TC) of the retina/retinal pigment epithelium (RPE) (retina/RPE TC), isolated from the eyes of 14 New Zealand albino rabbits, in which degenerative retinal lesion was modeled by a single subretinal injection of 0.01 mL of 0.9% sodium chloride solution, and 7 healthy rabbits without eye damage. The formation of retinal degeneration was judged on the basis of changes in morphofunctional parameters obtained during specialized ophthalmological research methods (optical coherence tomography, fundus autofluorescence, electroretinography) at follow-up periods of 1, 3 and 6 months. The level of expression of NLRP3 and CASP-1 genes in the retina/RPE TC was evaluated by reverse transcription polymerase chain reaction (RT-PCR). According to the results of the study, a statistically significant increase in NLRP3 gene expression (p &lt; 0.001) was noted in the retina/RPE TC of experimental animals, which may indicate the involvement of NLRP-3 inflammasome components in the development of neurodegenerative retinal lesions. At the same time, the expression of the gene encoding CASP-1 was detected only in the retina/RPE TC of experimental eyes and is probably due to local inflammatory mechanisms in the retinal tissue.The high level of NLRP3, CASP-1 mRNA, detected in all retina/RPE TC samples of experimental eyes at late stages of the experiment (3 and 6 months), allows us to assume the formation of mechanisms (for example, activated glial phenotype) that support inflammation in retinal tissue. This should be taken into account in actively developing transplantation methods for the treatment of retinal degeneration

EXAMINING LOCALLY EXPRESSED mRNA OF INFLAMMATORY MEDIATOR GENES IN A MODEL OF RETINAL PIGMENT EPITHELIUM ATROPHY AND RETINAL DEGENERATION INDUCED BY SUBRETINAL SALINE INJECTION IN RABBITS

Degenerative-dystrophic retinal diseases, particularly age-related macular degeneration (AMD), are now considered to be the lead cause of blindness and low vision in developed countries, with a steadily increasing trend. Recent publications provide evidence for the involvement of inflammatory mechanisms in TMD development and progression unveiled due to advances in innate and adaptive immunity research. However, the immunopathogenesis of atrophic AMD form, “geographic atrophy” (GA) remains largely unstudied. Objective: to investigate local mRNA expression of inflammatory cytokines IL-1β, IL-18, CCL2/MCP-1 in a model of RPE atrophy induced after subretinal injection of 0.9% sodium chloride solution in experimental rabbits. The investigation was carried out in tissue complex retina-RPE-choroid (TC) samples isolated from eyes of 23 albino New Zealand rabbits after modeling RPE atrophy by subretinal injection of 0.9% sodium chloride solution and 5 healthy rabbits lacking eye lesions. Animals in the experimental group (one week before surgical intervention, in the early period, and in the period of sustained RPE atrophy formation) and controls were subjected to optical coherence tomography (OCT) and ocular fundus autofluorescence (FAF). Evaluation of proinflammatory cytokine gene expression levels in TC was performed by RT-PCR. Results. Subretinal injection of 0.01 ml of 0.9% sodium chloride solution induced experimental RPE atrophy development in rabbits vs. control that was associated with multidirectional changes of IL-1β, IL-18, MCP-1/CCL2 gene mRNA expression. Three types of response in the TC, formed during development of atrophic changes and determined by the value of local cytokine gene expression were characterized: 1) hypo/ no response – decreased/no expression; 2) normal response – moderate increase; 3) hyper response – overexpression. 69.6% of animals with persistent atrophy had a moderate to hypertrophic increase in locally expressed mRNA MCP-1/CCL2, whereas 30% cases had significantly increased IL-1β mRNA expression – factors damaging the blood-retinal barrier and contributing to posterior segment immune privilege. It should be taken into account while developing new strategies for treatment of ophthalmic pathology, in particular the currently actively studied and tested options for RPE stem cell transplantation into subretinal space. The data obtained may be useful to investigate various types of RPE atrophy and develop new strategies of ophthalmopathology treatment in preclinical studies

Predictive model of small choroidal melanoma progression after eye-saving treatment based on clinical, morphometric and immunological parameters

Choroidal melanoma is a malignant tumor characterized by early metastasis and poor vital prognosis. Prognostic indexes for the tumor development are of importance, depending on various factors and making it possible to optimize therapeutic measures. Usage of present models for prediction of the uveal melanoma course enables optimal management of the patients with a malignant tumor upon primary admission, and to perform maximally efficient counseling. So far, however, a complex of clinical, morphometric and immunological indexes predictive for unfavorable course of initial choroidal melanoma following the eye-saving treatment remains not fully determined. Our purpose was to create a prognostic model for initial choroidal melanoma after eye-saving treatment, basing on clinical, morphometric and immunological parameters.We have performed examination and treatment of 31 patients with small choroidal melanoma (53.7 to 12.2 years old). To perform the analysis, we used clinical data (age, decreased vision, tumor localization, degree of pigmentation, presence of hemorrhages, orange pigmentation), morphometric indexes (intra- and subretinal exudate and disorganization of pigment of the retinal epithelium) and immunological parameters (serum levels of pro-inflammatory, pro-angiogenic, proliferative, metastasis-causing cytokines). Selection of variables for this model was based on assessment of significant differences between the groups with chorio-retinal scar (n = 14) and residual tumor and/or continued tumor growth (n = 17).Multivariate analysis with conditional exclusion of variables revealed prognostic significance with four markers: morphometric, i.e., disorganization of the pigment in retinal pigment epithelium – Z1 (rs = 0.455); immunological, increased blood serum concentration of hepatocyte growth factor (HGF) – Z2 (rs = 0.377); level of pro-inflammatory chemokine RANTES – Z3 (rs = 0.362), content of transforming growth factor (TGF-2â) – Z4 (rs = 0.431). A formula was calculated where P (z) is the value of the logistic function; Z, linear combination of symptoms; bo , intercept (free term), bi – regression coefficients for parameters Zi.P (z) = 1 : 1 + e – b0– b1z1– b2z2– b3z3– b4z4The logistic function increases monotonically and takes the values from 0 to 1 for any b and Z values [P∈ (0;1)]. If P (Z) is under the cutoff value, chorioretinal scar prognosis is predicted, at the higher values, a residual tumor or continued growth is expected. In ROC analysis, the area under the curve with this model was 0.891±0.11, thus providing good predictive quality.Usage of the predictive model is a possible solution for planning and correcting treatment strategy in the patients with small choroidal melanoma, in order to minimize complications and errors, and to ensure control of treatment

Features of effector lymphocyte subsets in patients with uveal melanoma in recurrent and chronic herpesvirus infection

The aim of the study is to conduct a comparative analysis of percentages for peripheral blood effector lymphocyte subsets in patients with uveal melanoma manifested by recurrent and chronic herpesvirus infection. There were 141 subjects enrolled: 70 patients with uveal melanoma, 38 patients with corneal ulcers and involvement of the uveal tract as well as 33 healthy donors. Immunophenotyping was performed by using laser flow cytometry with panel of monoclonal antibodies to differentiate lymphocyte subpopulations. IgM and IgG antibodies to herpesvirus infections were determined by using enzyme-linked immunosorbent assay on an automatic ELISA analyzer Lazurit (USA) with diagnostic kits of CJSC “Vector-Best” (Koltsovo). The data obtained showed that the absolute number of blood lymphocytes (CD45+) in patients with uveal melanoma did not differ from those in healthy donors. In contrast, patients with corneal ulcers and involvement of the uveal tract had this parameter increased. A decreased relative and absolute count of T cells (CD3+) in uveal melanoma, but increased absolute CD3+ number in inflammation was observed. No difference in relative and absolute content of the CD3+CD4+ helper/inducer subpopulation in patients with recurrent herpesvirus infections was found. Corneal ulcers in cancer patients revealed significantly increased absolute level of CD3+CD4+ helpers/inductor cells. Chronic herpesvirus infection in uveal melanoma patients showed increased relative and absolute number of cytotoxic T lymphocytes (CD3+CD8+). Recurrent herpesvirus infection was featured with decreased relative number of T lymphocytes (CD3+CD8+), upon inflammation, there was noted increased absolute and decreased relative number compared with healthy subjects. Double positive T cells increased in tumor and inflammation. B lymphocytes (CD19+) increased in melanoma and inflammation. The relative number of blood natural killer cells (CD16+CD56+) in uveal melanoma increased upon recurrent infection. Inflammation was coupled to decreased relative level of natural killer cells (CD16+CD56+). Melanoma showed no changes in CD4+/ CD8+ ratio; upon inflammation, its increase was noted in acute and chronic herpesvirus infections (p &lt; 0.05). The suppression of the immune system in uveal melanoma, restricting antiviral defense, was revealed. The data obtained seem to be important for development of personalized approaches to prognosis and treatment of patients with uveal melanoma

Исследование факторов регуляции экстраклеточного матрикса и биомеханических свойств корнеосклеральной оболочки при физиологическом старении и первичной открытоугольной глаукоме

PURPOSE: Comparative analysis of the biomechanical parameters of the fibrous tunic of the eyeball and extracellular matrix (ECM) characteristics in patients with suspected POAG, early-stage POAG and healthy elderly people, as well as control groups of various ages. METHODS: The study included 60 people aged 21 to 74 years. The first group consisted of 16 healthy young adults (n=16; mean age 26.3±5 years; “young" control group), the second group included 17 healthy elderly subjects (n=17; 69.2±4 years “age" control group) with no signs of ophthalmological pathology. The third group consisted of 17 people with suspected POAG (n=17; mean age 68.2±6 years; with IOP above 21 mm Hg for three consecutive measurements (average central corneal thickness) and absence of visual field defects on the threshold perimetry test). The fourth group consisted of 10 patients with early-stage POAG (n=10; mean age 67.6±5 years; lesion of one or both eyes). Therapy was discontinued 2 weeks prior to the study. Ophthalmic examination included both the standard (visometry, tonometry, biomicroscopy, gonioscopy, automatic static perimetry) and additional methods (laser scanning tomography). Investigation of the fibrous tunic biomechanical parameters was conducted using the Ocular Response Analyzer (ORA) («Reichert», USA). All subjects underwent lab tests. The content of the regulation of extracellular matrix factors, MMP-9 and TIMP-4, in the serum and tear fluid was determined by enzyme linked immunosorbent assay (ELISA; diagnostic test systems Bender MedSystems® («eBiosciences», Austria; «R & D Diagnostics Inc.», US). We investigated 60 tear fluid samples and 60 serum samples. Statistical processing was made in the SPSS program 17.0 (SPSS, Inc., Chicago, IL). Two independent groups were compared with the use of nonparametric U-test Mann-Whitney test. Correlation analysis was performed using the Spearman test (r). Differences were considered statistically significant at pЦЕЛЬ. Сравнительный анализ биомеханических параметров фиброзной оболочки глаза и показателей экстраклеточного матрикса (ЭКМ) у пациентов с подозрением на первичную открытоугольную глаукому (ПОУГ), начальной стадией ПОУГ и здоровых лиц пожилого возраста, а также в различных возрастных группах контроля. МЕТОДЫ. В исследование было включено 60 человек в возрасте от 21 года до 74 лет. Первую группу составили 16 здоровых людей молодого возраста (n=16; средний возраст 26,3±5 лет; «молодой контроль»), вторую группу - 17 практически здоровых лиц пожилого возраста (n=17; 69,2±4 года; «возрастной контроль») без признаков офтальмопатологии. В третью группу вошли 17 человек с подозрением на ПОУГ (n=17; средний возраст 68,2±6 лет). Четвертую группу составили 10 пациентов с начальной стадией ПОУГ (n=10; средний возраст 67,6±5 лет; поражение одного или обоих глаз). Офтальмологическое исследование включало помимо стандартных методов (визометрия, тонометрия, биомикроскопия, гониоскопия, статическая автоматическая периметрия) дополнительные методы (лазерная сканирующая томография). Исследование биомеханических параметров фиброзной оболочки было проведено при помощи аппарата Ocular Response Analyzer (ORA) («Reichert», США). Лабораторные исследования были проведены всем обследуемым лицам. В статье представлены результаты комплексного исследования факторов регуляции ЭКМ - матриксной металлопротеиназы - 9 (ММР-9), тканевого полиспецифичного ингибитора матриксных металлопротеиназ 4 типа (TIMP-4) в сыворотке крови (СК) и слезной жидкости (СЖ), а также биомеханических свойств корнеосклеральной капсулы (фактора резистентности роговицы (ФРР), корнеального гистерезиса (КГ) и соотношения КГ и ФРР (КГ/ФРР) у пациентов с подозрением на ПОУГ, начальной стадией ПОУГ и здоровых лиц различных возрастных групп. Содержание факторов регуляции внеклеточного матрикса ММР-9 и TIMP-4 в СК и СЖ определяли методом твердофазного иммуноферментного анализа (ELISA; диагностические тест-системы Bender MedSystems® «eBiosciences», Австрия; «R&D Diagnostics Inc.», США). Всего исследовано 60 проб СЖ и 60 проб СК. Статистическая обработка материала проводилась в программе SPSS 17.0 (SPSS, Inc., Chicago, il). Для сравнения двух независимых групп использовался непараметрический U-критерий Манна-Уитни. Корреляционный анализ проводился по Спирману (r). Различия считались статистически значимыми при

Features of systemic cytokine production in Behcet's disease associated with uveitis without ocular lesions

Behcet's disease (BD) is a systemic disease underlyed by chronic vasculitis. Hyperactivity of innate and adaptive immunity plays important role in its pathogenesis. Uveitis occurs in 30-70% of the patients, often recurring and reducing visual function. The objective of our work was to study the features of systemic production of immune mediators in BD patients, depending on presence and activity of uveitis. 116 BD patients were divided into 3 groups: (1) 41 patients with active uveitis (UA), (2) 64 subjects with uveitis remission (UR), (3) 11 uveitis-free BD patients (WU). Control group (CG) comprised 34 conditionally healthy people. Detection rate (%) and contents (pg/ml) were measured for IL-1β IL-2, IL-4, IL-5, IL-6, IL-12p70, IL-13, IL-18, IFNγ, CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL11/Eotaxin, СXCL1/GRO-α, CXCL8/IL-8, CXCL10/IP-10, CXCL12/SDF-1α, GM-CSF, TNFα in blood serum by means of multiplex analysis using MAGPIX analyzer (Luminex Corp., USA), Procarta Plex “Human Th1/Th2&amp;Chemokine Panel 20 plex” kits (Bioscience, Austria). TGF-P1, TGF-P2 levels were assayed by ELISA-test (“Vfector-Best”). All the BD patients showed high detection rates of CXCL1/GRO-α (but not its level) in comparison with CG. Detection rate and levels of IL-6, IL-8 were increased in 1st and 2nd BD groups, compared to CG. In UR, unlike UA and WU groups, IL-4 was detected more often than in CG. WU patients showed increased detection rate of only CXCL1/GRO -α. When compared with UA, WU patients had lower serum concentrations of IFNγ, MCP-1, IP-10, MIP-1a, SDF-1α, TGF-β1; UR patients also showed decreased serum levels of IL-18, Eotaxin, GRO-α, RANTES, TGF-β2. Our results indicate the importance of angiogenic and proinflammatory chemokines and cytokines in pathogenesis of BD uveitis, as well as imbalanced production of various immunomediators. Higher detection rates and levels of IL-6 and IL-8 in UA and UR patients may result from weak persistent intraocular inflammation, even upon relief of clinical symptoms, thus, probably, requiring therapeutic correction