Changes of the level of pro- and anti-inflammatory cytokines in tear of patients with advanced proliferative diabetic retinopathy and complicated primary cataract depending on the volume vitreoretinal surgery

Purpose. The aim is to estimate the content of pro- and anti-inflammatory cytokines (IL-1β, IL-8, IL-10, MCP-1, ICAM-1, VEGF) in tear of patients with advanced proliferative diabetic retinopathy and complicated primary cataract after phacoemulsification surgery and IOL implantation with vitreoretinal surgery accomplished at once in comparison with vitreoretinal surgery only. Material and methods. 34 cases of surgery treatment of patients with PDR and complicated primary cataract were enrolled. This patients were divided into two groups depending on the treatment tactics. In the 1st group patients were subjected to a two–step surgical procedure: vitreoretinal surgery (VRS) with silicone oil tamponade performed as the 1st step in their treatment; followed by the 2nd step, phacoemulsification surgery and silicone oil removal, and the IOL implantation, respectively. In the 2nd group phacoemulsification performed simultaneously with vitreoretinal surgery: phacoemulsification, IOL implantation, vitreoretinal surgery with silicone oil tamponade. The second step differed in the removal of silicone oil from the vitreous cavity. On the 2nd day after the 1st step surgery and before surgical treatment the tear samples of the patients of both groups have been examined. Results. A concentration of the following cytokines: IL-8, MCP-1, ICAM-1 in the 2nd group was 2,5-5 times higher than in the 1st group. Conclusion. The research revealed that the patients with advanced PDR are accurately determined by the increased concentration of IL-8, MCP-1, ICAM-1 in tear after phacoemulsification surgery and IOL implantation with vitreoretinal surgery accomplished at once in comparison with vitreoretinal surgery only. Keywords: cytokines, diabetic retinopathy, cataract, vitreoretinal surgery.

From genes polymorphisms to mucosal expression of cytokines: evaluating IL-23/IL-17 axis in adult patients with gastritis

Background and Objective: Chronic inflammation is the typical sign of gastritis that may shift into gastric cancer. IL- 17A and IL-17F as a novel inflammatory cytokines subset of CD4+Th play the main role in inflammation. A key cytokine receptor in the inflammatory IL-17/IL-23 axis, the interleukin 23 receptor (IL23R), may be related to gastritis. We evaluated the correspondence between IL-17A G197A, IL-17F A7488G and IL23R+2199 A/C polymorphisms with TGF-β1, IL-6, IL-17, IL-21 and IL-23 mucosal mRNAs expression in uninfected H. Pylori (HP) chronic gastritis patients. Materials and Methods: Total RNA and genomic DNA were separated from gastric biopsies of 44 patients with gastritis. Subsequently, mucosal mRNAs expression of TGF-β1, IL-6, IL-17, IL-21 and IL-23 were assessed by real-time PCR. To polymorphisms determination of IL-17A G197A, IL-17F A7488G and IL-23R +2199A/C the PCR-RFLP was used in gastric biopsies. Results: Results point that IL-17A G197A, IL-17F A7488G and IL23R +2199A/C polymorphisms did not influence the mucosal expression of TGF-β1, IL-6, IL-17 and IL-21 (p> 0.05). In an opposite result, we don’t find a correspondence between IL-17A G197A, IL-17F A7488G polymorphisms and mucosal expression of IL-23 (p> 0.05). In a contrary, we found a correlation between IL23R +2199A/C polymorphism and mucosal expression of IL-23 in patients with chronic gastritis (p< 0.05). Conclusion: These findings propose that IL23R +2199A/C polymorphism may change the mucosal expression of IL-23 pattern in patients with gastritis disease in the absence of HP, but to support the conclusion, more research may be required. Keywords: Cytokines; polymorphism; gastritis; IL-23, IL-17.

NITROGEN OXIDE ROLE IN MANIFESTATION OF RESPIRATORY EFFECTS OF INCREASED EXOGENOUS IL-1Β LEVEL IN BLOOD-VASCULAR SYSTEM

The purpose of the study is to identify the role of nitrergic mechanisms in the ability of the pro-inflammatory cytokine IL-1β to influence the respiration pattern and hypoxic ventilation response. Materials and Methods. The experiments were performed on 42 anesthetized rats. To conduct an inhibitory analysis of the nitric oxide role in the manifestation of IL-1β respiratory effects, the authors used a non-selective inhibitor of NO-synthases of Nitro-L-arginine-methyl ether (L-NAME), and a highly specific inhibitor of inducible nitric oxide synthase, aminoguanidine bicarbonate. The hypoxic ventilation response was evaluated by a rebreathing method with a hypoxic gas mixture before and after intravenous administration of human recombinant IL-1β. Pneumatic tachometry was used to register the parameters of external respiration. Results. Intravenous administration of IL-1β has an activating effect on respiration and causes an increase in tidal volume by 36±5.2 %, minute respiration volume by 23±3.8 % and average inspiratory flow rate by 20±3.0 %. However, an increase in IL-1β systemic level decreases the ventilation response to hypoxia. Inhibition of NO-synthase activity with both L-NAME and aminoguanidine reduces IL-1β respiratory effects. Conclusion. One of the mechanisms to implement the respiratory effects of the key pro-inflammatory cytokine IL-1β in case of increase in its circulating level is an increase in the synthesis of nitric oxide with vascular endothelium cells. Keywords: cytokines, interleukin-1β, ventilation, ventilation response to hypoxia, hypoxic chemoreflex, nitric oxide. Цель исследования. Выявление роли нитрергических механизмов в способности провоспалительного цитокина ИЛ-1β оказывать влияние на паттерн дыхания и гипоксический вентиляционный ответ. Материалы и методы. Эксперименты выполнены на 42 наркотизированных крысах. Для проведения ингибиторного анализа роли оксида азота в проявлении респираторных эффектов ИЛ-1β использовались неселективный ингибитор NO-синтаз L-нитро-аргинин-метилэфира (L-NAME), а также высокоспецифичный ингибитор индуцибельной синтазы оксида азота аминогуанидина бикарбоната. Гипоксический вентиляционный ответ оценивался методом возвратного дыхания гипоксической газовой смесью до и после внутривенного введения человеческого рекомбинантного ИЛ-1β. Для регистрации параметров внешнего дыхания использовался метод пневмотахометрии. Результаты. Показано, что внутривенное введение ИЛ-1β оказывает активирующее влияние на дыхание, вызывая увеличение дыхательного объема на 36,0±5,2 %, минутного объема дыхания – на 23,0±3,8 % и средней скорости инспираторного потока – на 20,0±3,0 %. Вместе с тем повышение системного уровня ИЛ-1β вызывает ослабление вентиляционного ответа на гипоксию. Ингибирование NO-синтазной активности с помощью как L-NAME, так и аминогуанидина ослабляет респираторные эффекты ИЛ-1β. Выводы. Одним из механизмов реализации респираторных эффектов ключевого провоспалительного цитокина ИЛ-1β при повышении его циркулирующего уровня является усиление синтеза оксида азота клетками сосудистого эндотелия. Ключевые слова: цитокины, интерлейкин-1β, вентиляция, вентиляционный ответ на гипоксию, гипоксический хеморефлекс, оксид азота.

Serum Cytokines in Erythema Nodosum Leprosum Versus Non-Reactional Leprosy: A Systematic Review and Meta-analysis

Background. Erythema nodosum leprosum is an immune-mediated complication of leprosy whose underlying mechanism has not yet been fully elucidated, making management difficult.Objectives. To determine the serum cytokine profile of ENL compared to non-reactional leprosy states. Methods. An open literature search was performed using MEDLINE, Cochrane Library, TRIP and HERDIN electronic databases using the keywords ("cytokines" or “inflammatory mediators”) and (“erythema nodosum leprosum” or “ENL”) and (“leprosy” or “lepra”). Studies were selected by two independent review authors. Risk of bias was assessed using the Newcastle-Ottawa Scale and statistical analysis was performed using RevMan 5.3 software. Results. Eight cross-sectional studies with 197 participants were included. Meta-analysis showed that both serum IL-17 and serum IFN-γ were significantly decreased (Z 2.39, p = 0.02 and Z 2.74, p = 0.01, respectively) in ENL compared to non-reactional states. However, for IL-1β, IL-6, IL-10, IL-22, TNF-α and TGF-β, no significant differences were found between the two groups. Conlusion. ENL appears to be an exacerbation of the Th2 cytokine response seen in the lepromatous pole of leprosy. However, despite pooling of data, sample sizes remain small resulting in significant heterogeneity. Future studies involving large sample sizes and investigating a wider range of cytokines are encouraged.