Contents of chemokines in lacrimal fluid of the patients with diabetic retinopathy and type 2 diabetes mellitus

Diabetic retinopathy is a serious microvascular complication of diabetes mellitus with chemokines playing an important pathogenetic role. However, the studies of chemokines in lacrimal fluid of the patients with diabetic retinopathy and type 2 diabetes mellitus (T2DM) are rarely performed. The aim of the study was to analyze the content of chemokines in lacrimal fluid of patients suffering from diabetic retinopathy and T2DM. When determining the concentration of chemokines in the lacrimal fluid, two clinical groups were formed: the main group of 56 elderly patients suffering from diabetic retinopathy and T2DM, and a control group of 48 age-matched persons with T2DM, however, without diabetic retinopathy. The diagnosis of diabetic retinopathy was performed after comprehensive ophthalmological examination using various modern techniques and applying the criteria of the All-Russian Association of Ophthalmologists “Diabetes mellitus: diabetic retinopathy, diabetic macular edema”. The chemokine levels in the lacrimal fluid were determined in the morning on the MAGPIX device (USA). The changed contents of chemokines was shown in lacrimal fluid of patients with diabetic retinopathy and T2DM, in comparison with patients suffering from T2DM in absence of diabetic retinopathy. In elderly patients with diabetic retinopathy and T2DM, a decreased content of GROα/ CXCL1, RANTES/CCL5 and MIP-1α/CCL3 was revealed in lacrimal fluid, at a statistically significant difference as related to controls. At the same time, the content of GROα/CXCL1 chemokine in lacrimal fluid was decreased most significantly, (38.24±2.57 in the main group versus 13.61±1.74 pg/mL in the comparison group). The level of RANTES/CCL5 decreased to 0.92±0.16 pg/mL versus 1.69±0.18 pg/mL (p < 0.001); MIP-1α/CCL3, to 2.06±0.71pg/mL versus 3.79±0.64 pg/mL, respectively. However, the proportion of chemokines in the lacrimal fluid of patients with diabetic retinopathy and T2DM was significantly inceased in  all  cases.  This  finding  concerns  MCP-1/CCL2,  IP-10/CXCL10,  and  SDF1α/CXCL12.  The  content  of IP-10/CXCL10 in lacrimal fluid increased to maximal values of 38.24±2.57 pg/mL in the patients with diabetic retinopathy and T2DM compared with 13.61±1.74 pg/mL in patients with diabetes mellitus without diabetic retinopathy, MCP-1/CCL2 to 742.34±0.89 pg/mL compared to 633.72±0.64 pg/mL, respectively; SDF1α/ CXCL12, to 264.78±7.82 pg/mL compared to 213.49±6.08 pg/mL. In addition, the interrelations between studied chemokines in patients with diabetic retinopathy and type 2 diabetes mellitus are more pronounced than in comparison group as confirmed by large number of correlations in the main group. The results obtained expand the knowledge on the effects of chemokines in lacrimal fluid upon development of diabetic retinopathy

Interleukins in lacrimal fluid and diabetic retinopathy

The leading role of diabetic retinopathy is considered the main causal factor of decreased visual acuity in the able-bodied and elderly ages determines its clinical relevance, including immunological aspects of pathogenesis to improve the diagnosis and treatment of this ophthalmic pathology. Currently, changes in lacrimal fluid interleukins in elderly patients suffering from diabetic retinopathy have not been sufficiently studied. The aim of our work was to study the content of pro-inflammatory and anti-inflammatory interleukins in lacrimal fluid in elderly patients with diabetic retinopathy.The lacrimal fluid interleukins were analyzed in two clinical groups: the main group was represented by 72 elderly patients with diabetic retinopathy, and the control group included 64 patients of the same age with type 2 diabetes mellitus without diabetic retinopathy. The diagnosis of diabetic retinopathy was assessed from the criteria of Clinical Recommendations “Diabetes mellitus, diabetic retinopathy, diabetic macular edema” issued by the All-Russian Association of Ophthalmologists based on the results of a comprehensive ophthalmological examination. In the lacrimal fluid taken from all patients, the content of various pro- and anti-inflammatory interleukins was studied by solid-phase enzyme immunoassay using R&D Diagnostic Inc. (USA) test systems. Arithmetic average values, their errors, relative risk factors and confidence intervals were calculated, and their significance was evaluated. We have obtained following results: a statistically significant increase of most proinflammatory interleukins was detected in the lacrimal fluid of patients with diabetic retinopathy. In particular, expression of IL-6 was increased to 142.9±7.8 pg/ml among the patients with diabetic retinopathy versus 6.8±0.7 pg/ml in the comparison group, IL-3 was increased to 2.4±0.3 pg/ml versus 0.3±0.05 pg/ml, respectively (p < 0.001). The production of other pro-inflammatory interleukins at the local site has also increased, except of IL-7. However, the concentration of IL-4 and IL-10 was significantly decreased in the patients with diabetic retinopathy, with even higher increase of IL-10 (4.3±0.5 pg/ml versus 11.7±2.3 pg/ml, p < 0.001). The relative risk values were the highest for IL-6 (7.824), at the reliable confidence interval of 7.5388.261; for IL-3 these values comprised 3.269 (CI 3.084-3.721). High relative risk values were also established for IL-8, IL-5 and IL-1α2. The relative risk of developing diabetic retinopathy by almost 2 times was associated with higher contents of IL-8 in the lacrimal fluid (statistically significant confidence interval of 1.728-2.432 (p < 0.01); for IL-5 it was 1.748 (confidence interval of 1.462-2.194 (p < 0.01); for IL-1α2 it comprised 1.718 (confidence interval of 1.524-2.137, p < 0.001). These findings suggest an association of the abovementioned interleukins and development of diabetic retinopathy. The established patterns expand modern views concerning immunopathogenesis of diabetic retinopathy, involving the interleukins of lacrimal fluid

Diagnosis and prediction ofprimary open-angle glaucoma by the level of local cytokine

The incidence of glaucoma is rather high in different countries, being the leading cause of visual loss in the population, thus presuming relevance of the search for new and informative methods of diagnosing this disease. According to modern views, changes of local interleukins seem to be important for the glaucoma pathogenesisis. The aim of present study was to improve diagnosis and prognosis of primary open-angle glaucoma on the basis of information content of interleukins at the local level. The study was conducted on the basis of S. Fyodorov Intersectoral Research and Technology Complex “Eye Microsurgery”. The main group of patients consisted of 109 patients with primary open-angle stage II glaucoma. The age of glaucoma patients ranged from 58 to 75 years with a median of 62.4±2.5 years. The control group consisted of 52 persons without glaucoma at present and in past, the average age of which did not differ significantly from the members of the main group, i.e., 59.6±2.8 years (p > 0.05). The studies of interleukin content in lacrimal fluid was carried out by means of the Multiscan enzyme immunoassay (Finland) using common sandwich-variant of solid-phase enzyme immunoassay with R&D Diagnostic Inc. test systems (USA). The diagnostic significance (informativeness) for local interleukins was calculated according to the generally accepted formula. Statistically significant changes in the levels of lacrimal interleukins were revealed in the patients with primary open-angle glaucoma. The highest increase in the content of local interleukins was found for IL-2 (8.4-fold) and IL-17 (8.3-fold). The content of IL-8 was also increased significantly in the lacrimal fluid of patients with primary open-angle glaucoma. However, the changes in the studied local anti-inflammatory interleukins proved to be multidirectional: the level of IL-4 in the formed primary open-angle glaucoma was significantly increased, and the level of IL-10, on the contrary, was decreased. Evaluation of diagnostic significance by the local interleukin levels showed the maximal informative value for IL-2 (J = 637.4), and IL-17 (J = 612.8), which indicates their leading role for diagnostics of primary open-angle glaucoma. High level of information content is typical for IL-8 (J = 572.5). Using regression analysis for the most informative interleukins in lacrimal fluid, we have developed a mathematical model that provides a high-probability prediction (P < 0.001) of primary open-angle glaucoma. Lacrimal concentrations of IL-2, IL-7 and IL-8 are the most informative indexes of lacrimal fluid for the diagnosis and prediction of primary open-angle glaucoma

Evaluation of blood interleukin levels and their correlations in the patients with diabetic retinopathy with mild and moderate cognitive impairment

Systemic immunological disorders are associated with various geriatric conditions, including cognitive dysfunction. However, in patients with diabetic retinopathy, the changes of blood interleukin profile were studied without considering the severity of cognitive impairment. The aim of this study was to analyze blood plasma levels and intercorrelations of interleukins in the patients with diabetic retinopathy accompanied by mild and moderate cognitive impairment. Fifty-four elderly patients with diabetic retinopathy and mild cognitive impairment, and 62 patients with diabetic retinopathy and moderate cognitive disorders underwent inpatient examination and treatment at the Tambov branch of the S. Fedorov Center of Eye Microsurgery over 2021-2022. The interleukins contents in blood plasma were studied by enzyme immunoassay using the Protein Contour kit, including IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-17, IL-18. The diagnostics of diabetic retinopathy was based on comprehensive ophthalmological examination, according to the Clinical recommendations of the Society of the Russian Association of Ophthalmologists «Diabetes mellitus: diabetic retinopathy, diabetic macular edema». Cognitive functions were assessed according to a valid Mini- Mental-State-Examination scale. It has been shown that the patients with diabetic retinopathy and moderate cognitive impairment have a significantly increased level of all the studied proinflammatory interleukins, as compared to similar cohort with diabetic retinopathy accompanied by a mild cognitive impairment. In mild cognitive disorders, the content of IL-6 in blood plasma was higher (24.4±2.1 pg/mL versus 5.1±0.8 pg/mL, p < 0.001). Development of moderate cognitive impairment in the patients with diabetic retinopathy was also accompanied by a statistically significant increase of plasma IL-8 to 36.7±3.5 pg/mL versus 10.5±2.3 pg/mL with mild cognitive impairment; IL-17, to 21.9±1.8 pg/mL versus 8.5±1.1 pg/mL, respectively. Concentrations of anti-inflammatory interleukins in blood plasma of the patients with diabetic retinopathy and moderate cognitive dysfunction were significantly decreased, i.e., IL-4 to 2.1±0.3 pg/mL versus 3.4±0.5 pg/mL in cases of mild mental deterioration; IL-10, to 8.7±0.5 pg/mL versus 15.4±1.3 pg/mL, respectively. A sufficient correlation was shown between the levels of systemic interleukins and moderate cognitive disorders in the patients with diabetic retinopathy. For the proinflammatory interleukins in cases of moderate cognitive impairment, an inverse correlations with IL-1β (r = -0.336; p = 0.021), IL-6 (r = -0.584; p = 0.019), IL-8 (r = -0.469; p = 0.006), and with IL-17 (r = -0.348; p = 0.018) were shown. The content of IL-4 and IL-10 in blood plasma of the patients with diabetic retinopathy correlated with moderate cognitive impairment at a significant level of r = +0,407 (p = 0.016) and r = +0.359 (p = 0.008), respectively. In mild cognitive impairment, the correlations with fewer numbers of interleukins were revealed, i.e., IL-1β, IL-6, IL-8 and IL-10, and exhibit weaker connections, except of IL-6 (a moderate connection level). Development of moderate cognitive impairment among the patients with diabetic retinopathy may be caused by increase in IL-1β, IL-6, IL-8, IL-17, and a decrease in IL-10

Dissociation of biological age and blood interleukins in patients aged 45–59 years with diabetic retinopathy in type 2 diabetes mellitus

Background. The development of diabetic retinopathy is favoured by immunological factors such as interleukins (IL) and chemokines. However, analysis of blood interleukins in patients aged 45–59 years with diabetic retinopathy in type 2 diabetes mellitus, who have biological age acceleration, has not yet been presented in publications. The aim of the research. To study the content of blood interleukins in patients aged 45–59 years with diabetic retinopathy in type 2 diabetes mellitus, who have an excess of biological age over chronological age. Materials and methods. 241 patients aged 45–59 years with diabetic retinopathy in type 2 diabetes mellitus were examined in a clinical setting. Biological age acceleration over chronological age was found in 148 patients, biological and chronological age concorded in 51 patients. The content of interleukins in the blood was studied in all patients using an enzyme-linked immunoassay. Results. The concentration of blood interleukins in patients with biological age exceeding chronological, compared with patients aged 45–59 years with concordance of biological and  chronological age, was statistically significantly different for most blood interleukins and especially for IL-6, the concentration of which was  20.8  ±  1,2  pg/ml versus 3.9  ±  0.6  pg/ml, respectively (p  <  0.001). IL-13, IL-17 were significantly increased among patients with biological age acceleration over chronological; their concentrations were 2.1 ± 0.4 and 16.5 ± 0.6 pg/ml versus 0.5 ± 0.2 and 7.9 ± 0.7 pg/ml in the comparison group (p < 0.001). In contrast, IL-4 and IL-10 levels were higher in patients aged 45–59 years with diabetic retinopathy in type 2 diabetes mellitus and with concordance of biological and chronological age. Conclusion. IL-6, IL-8, IL-13, IL-17, IL-4 and IL-10 may serve as markers of biological age dissociation in patients aged 45–59 years with diabetic retinopathy in type 2 diabetes mellitus

Dynamics of humoral immunity in gingival fluid during combined immunotherapy in pediatric patients with exacerbation of chronic granulomatous periodontitis

Chronic granulating periodontitis among children has a high prevalence, which determines the relevance of its research, medical and social significance. The exacerbation of the disease is accompanied by various disorders in the immune system and, above all, at the local level. However, changes in local humoral immunity in children with exacerbation of chronic granulating periodontitis (CGP) have not been studied. Impact of modern immunomodulators and, in particular, Derinat, on pathological changes of local parameters of humoral immunity was not analyzed in pediatric patients with this disorder.The aim of this work is to study local humoral immunity parameters during CGP exacerbation in children and on the background of combined therapy with Derinat, Unidox-Solutab, and Tycveolum (oil extract from pumpkin seeds).The analysis of immunological disorders in gingival fluid was performed in 93 children aged 12-14 years with exacerbation of chronic granulating periodontitis, who underwent examination and treatment in Belgorod city pediatric dental clinic, and at the Department of Pediatric Dentistry of Belgorod State National Research University in 2013-2015. The patients included in the study were divided into 2 groups: control group (n = 48), receiving conventional treatment, and the main group (n = 45), who, in addition to standard therapy, were treated with Derinat, Unidox-Solutab and Tycveolum. Contents of immunoglobulins in gingival fluid were determined by turbidimetric method using the Microlab-300 photometer. Lysozyme and lactoferrin were studied by solid-phase enzyme immunoassay.Exacerbation of chronic granulating periodontitis in childhood is associated with a representative decrease of sIgA, IgA, lysozyme and lactoferrin in gingival fluid, and increased levels of IgM and IgG. Upon treatment with innovative therapy, including derinate, as one of the components, in CGP patients, there was a significant improvement of immune parameters on the 14th day of observation. Normalization of all studied parameters of local immunity was noted in the patients of main group by the 30 th day of observation. Meanwhile, only some immunological parameters reached normal reference values in the control group of patients. Conclusion. The identified new mechanisms of Derinat effects upon humoral immunity and it’s effective use during exacerbation of chronic granulomatous periodontitis in children

Optimization of the drainage system of overburden dumps using geofiltration modeling

The article describes the assessment of the predicted water flows at the site of the projected rock dumps, which was carried out using geofiltration modeling. When developing the model, we used actual data on capacities, filtration coefficients and water capacity, roof and sole marks of the selected aquifers, precipitation infiltration, as well as the projected dumps are located on the slope surfac

Immune pleiotropic effect of telmisartan in arterial hypertension

Arterial hypertension (AH) is among the life-threatening diseases and requires permanent antihypertensive therapy, including telmisartan. However, the effect of telmisartan upon systemic interleukin profile in elderly hypertensive patients requires further study, due to the limited data on previously analyzed interleukins. The aim of our study was to evaluate the immune pleiotropic effect of telmisartan upon miultiple pro- and anti-inflammatory blood interleukins in the patients with hypertension. The study included examination of 74 patients aged 60-74 years suffering from hypertension treated with telmisartan (80 mg/day in the morning time). The immune response to telmisartan assessed by the blood contents of different interleukins was evaluated following 6 months of treatment. These markers were determined by flow cytometry using “Becton Dickinson FACS Canto 2” device (USA). The pleiotropic immune effect of telmisartan upon the interleukin profile in hypertensive patients aged 60-74 was established by statistically significant changes in multiple pro-inflammatory and anti-inflammatory interleukins. Following 6 months of telmisartan therapy, the patients with arterial hypertension have shown a statistically significant decrease in blood cytokines, i.e., IL-1 в was reduced to 8.1±0.6 pg/ml vs initial 10.5±0.8 pg/ml; IL-2, to 8.6±0.8 pg/ml vs initial 11.8±1.1 pg/ml; IL-6, to 18.4±0.5 pg/ml vs initial 21.2±0.7 pg/ml; IL-8, to 3.5±0.6 pg/ml vs 5.4±0.5 pg/ml. We have also revealed a statistically significant decrease of blood TNFα levels to 5.3±0.5 pg/ml versus initial 6.8±0.4 pg/ml in the elderly patients with hypertension after 6 months of antihypertensive therapy with telmisartan. Moreover, the levels of pro-inflammatory systemic interleukins and, especially, IL-4 showed an increase from 4.6±0.5 pg/ml to 7.0±0.6 pg/ml in the course of telmisartan therapy in these patients. In summary, one may suggest that telmisartan exerts a significant immune pleiotropic effect in the patients with hypertension, confirmed by the systemic changes of interleukin contents. The pleiotropic effects of telmisartan have been established in patients with arterial hypertension, expressed as a significant decrease in IL-1, IL-2, IL-6, IL-8, TNFα levels, along with increased IL-4 and IL-10 contents. The results obtained showed a significant pleiotropic effect of telmisartan in the patients with arterial hypertension upon several interleukins, thus expanding the role of immune inflammation in this disorder, as well as its reversal with telmisartan therapy

Informative significance of serum cytokines and their importance for development of metabolic syndrome with arterial hypertension in elderly persons

Metabolic syndrome (MS) is among the main public health challenges worldwide, leading to significant labor losses, increased costs for treatment and rehabilitation of the patients. The aim of the present study was to identify the informative serum interleukins, by determining the odds ratio in elderly patients with MS and hypertension. The main group of 86 patients with MS and arterial hypertension (AH) aged 60-75 years was examined under clinical conditions. The inclusion criteria were as follows: age of 60-75 years, presence of MS, primary hypertension (grade II-III), absence of acute myocardial infarction, malignant neoplasms, disorders of cerebral circulation, kidney failure over last 6 months. Diagnostics of MS and hypertension was carried out in accordance with Expert Guidelines from the Russian Research Society of Cardiology on the MS Diagnosis and Treatment. Our first study of a large range of serum interleukins in elderly patients with MS and hypertension allowed us to reveal the inversely directed changes in pro- and anti-inflammatory cytokine contents. Combined AH/MS in elderly persons is accomplished by sufficient increase of the most proinflammatory cytokines, and vice versa, by significant decrease in anti-inflammatory cytokines in blood serum. This finding clearly points to importance of immunological regulatory systems for initiation of AH with MS at older age. Pro- and anti-inflammatory serum interleukins are actively involved into the AH/MS development in elderly accompanied by their pronounced imbalance. The mentioned immune reactions could underlie the MS/AH condition. High risk of this disorder is connected with changed production of proinflammatory cytokines (IL-8, IL-1β), like as anti-inflammatory serum interleukins (IL-4, IL-10), with predominance of the former. The above interleukins should be considered dominant diagnostic markers of AH/MS in elderly persons. Measurement of serum interleukins and discriminant-based approach allows highly reliable differentiation of elderly patients with AH/MS from similar individuals without this disorder

Infiornativity lacrimal fluid interleukins in diagnostics and development of angle-closure glaucoma in elderly subjects

An increased percentage of the elderly subjects in pattern of contemporary society, along with other causes and risk factors, is accompanied by rise in the incidence of glaucoma. By 2020, according to international studies it is expected that prevalence of glaucoma patients in the world would increase up to 80 million subjects. Among the elderly, glaucoma is a common pathology, which development is associated with local disturbances in interleukin profile. However, the features of the latter in patients with primary closed-angle glaucoma in the elderly were poorly examined. Studies of local interleukin status were conducted mainly in patients with suspected or initial manifestations of primary open-angle glaucoma. The features of lacrimal fluid interleukin shift in a target group of elderly patients suffering from stage II primary closed-angle glaucoma virtually gained no attention. In addition, a limited range of local interleukins in patients with such pathology in previous studies was examined. In addition, informativity of lacrimal fluid interleukins in elderly glaucoma patients was not assessed too based on objective methods. The aim of the current study was to outline features and informativity of local interleukin profile indicators in 58 elderly patients with primary closed-angle glaucoma stage II, aged 60—74 years (main group) and 27 age-matched elderly subjects lacking such pathology. The level of interleukins in the lacrimal fluid was determined with the enzyme immunoassay “Multiscan” analyzer (Finland) by using sandwich ELISA (R&D Diagnostic Inc., USA). Informativity of measuring various interleukins was calculated according to the generally accepted formula. It was found that local interleukin profile in elderly patients with primary closed-angle glaucoma was mainly featured with increased amount of IL-2, IL-17, IL-8, but decreased IL-10. Hence, such local interleukins displayed peak informativity. The data obtained should be used in the diagnostics and treatment of such pathology, as well as of applied importance to unveil novel mechanisms behind development, diagnostics and corroboration for selective immuno-tropic therapy of primary closed-angle glaucoma