Interleukin IL-6 Research Articles

Clinical and immunological efficiency of dry carbon dioxide baths in patients with asthma and obesity at the ambulatory-polyclinic stage of rehabilitation

Introduction. An important part in the rehabilitation treatment of patients with asthma associated with obesity is the ambulatory-polyclinic stage of rehabilitation that includes drug and physiotherapeutic treatment. Recently, dry carbon dioxide baths (DCDB) are increasingly used.Aim. is to assess the clinical and immunological efficiency of DCDB in the complex rehabilitation treatment of patients with asthma and obesity at the ambulatory-polyclinic stage of rehabilitation.Materials and methods. The study included 60 patients with asthma and obesity admitted to the departments of medical rehabilitation and clinical examination of scientists of the Medical Association of FEB RAS. Patients of the main group (30 subjects) received DCDB and drug therapy. Patients of the comparison group (30 subjects) received only drug therapy. The DCDB procedures were carried out using the “Reabox” device at CO2 concentration of 15-20%, a temperature of 28-30ºC, 10 procedures. The changes in symptoms, ACQ-5 test, and respiratory function were assessed. The parameters of cellular immunity CD3+, CD4+, CD8+, CD16+, CD19+ and the levels of tumor necrosis factor (TNFα), interleukins (IL) IL-2, IL-4, IL-6, IL-10, IL-17A in the blood were analyzed.Results. The achievement of asthma control took less time in patients of the main group. The improvement of bronchial patency was evidenced by the positive dynamics of spirometric indices. After DCDB therapy, an increase in suppressive activity of the cellular immunity, a decrease in the levels of pro-inflammatory cytokine IL-4, IL-17A were revealed. The TNF-α/IL-10 ratio statistically significantly changed due to the increase in the level of anti-inflammatory cytokine IL-10. In the comparison group, the positive dynamics was less pronounced.Conclusion. The use of DCDB increases the clinical and immunological efficiency of the rehabilitation of patients with asthma and obesity at the ambulatory-polyclinic stage. The clinical effect is associated with immunocorrective action, which allows achieving control of the disease in a shorter period of time.

Immunometabolic bases of type 2 diabetes in the severity of COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 and type 2 diabetes (T2D) have now merged into an ongoing global syndemic that is threatening the lives of millions of people around the globe. For this reason, there is a deep need to understand the immunometabolic bases of the main etiological factors of T2D that affect the severity of COVID-19. Here, we discuss how hyperglycemia contributes to the cytokine storm commonly associated with COVID-19 by stimulating monocytes and macrophages to produce interleukin IL-1β, IL-6, and TNF-α in the airway epithelium. The main mechanisms through which hyperglycemia promotes reactive oxygen species release, inhibition of T cell activation, and neutrophil extracellular traps in the lungs of patients with severe SARS-CoV-2 infection are also studied. We further examine the molecular mechanisms by which proinflammatory cytokines induce insulin resistance, and their deleterious effects on pancreatic β-cell exhaustion in T2D patients critically ill with COVID-19. We address the effect of excess glucose on advanced glycation end product (AGE) formation and the role of AGEs in perpetuating pneumonia and acute respiratory distress syndrome. Finally, we discuss the contribution of preexisting endothelial dysfunction secondary to diabetes in the development of neutrophil trafficking, vascular leaking, and thrombotic events in patients with severe SARS-CoV-2 infection. As we outline here, T2D acts in synergy with SARS-CoV-2 infection to increase the progression, severity, and mortality of COVID-19. We think a better understanding of the T2D-related immunometabolic factors that contribute to exacerbate the severity of COVID-19 will improve our ability to identify patients with high mortality risk and prevent adverse outcomes.

Investigation of the inflammatory and oxidative stress-inducing effects of deoxynivalenol and T-2 toxin exposure in non-tumorigenic human intestinal cell model

Fungi in the Fusarium genus produce trichothecene mycotoxins including deoxynivalenol (DON) and T-2 toxin which may elicit their damaging effects on the gastrointestinal tract following the consumption of contaminated cereal-based foods. The aim of our study was to evaluate the effects of these commonly occurring fusarotoxins alone and in combination using the human, non-cancerous intestinal epithelial cell line HIEC-6. Based on our experimental data, 24 h after treatment with fusarotoxins, hydrogen peroxide levels, intracellular oxidative stress and the amounts of inflammatory interleukins IL-6 and IL-8 significantly increased. Cell membrane localization of the tight junction protein claudin-1 decreased, whereas distribution of occludin remained unchanged. Taken together, the HIEC-6 cell line appears to be a suitable experimental model for monitoring the combined effects of mycotoxins at the cellular level including changes in the redox states of cells.

Diacerein Inhibits Myopia Progression through Lowering Inflammation in Retinal Pigment Epithelial Cell.

Myopia is a highly prevalent refractive disorder. We investigated the effect of diacerein on monocular form deprivation (MFD) in hamsters as a possible therapeutic intervention. Diacerein is an anthraquinone derivative drug whose active metabolite is rhein. Diacerein or atropine was applied to the MFD hamsters, and their refractive error and axial length were measured after 21 days. The refractive error (control: −0.91 ± 0.023, atropine: −0.3 ± 0.08, and diacerein: −0.27 ± 0.07 D) and axial length (control: 0.401 ± 0.017, atropine: 0.326 ± 0.017, and diacerein: 0.334 ± 0.016 mm) showed statistically significant differences between control, atropine-treated, and diacerein-treated MFD eyes. Furthermore, we determined the level of transforming growth factor-beta- (TGF-) β1, matrix metalloproteinase- (MMP-) 2, type I collagen, interleukin- (IL-) 6, IL-8, and monocyte chemoattractant protein- (MCP-) 1 in the retina. Atropine and diacerein suppressed levels of the myopia-related TGF-β1 and MMP-2 while increasing type I collagen expression. They also inhibited the interleukin IL-6, IL-8, and MCP-1 levels. Diacerein reduced the IL-6, IL-8, and MCP-1 expression in ARPE-19 cells. Furthermore, diacerein inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. This suggests that diacerein has a therapeutic effect on myopia and is a potential treatment option.

Does thyroid dysfunction influence inflammatory mediators in experimental periodontitis?

Objective. The aim of the present study was to investigate the presence of inflammatory mediators in rats with only periodontitis and periodontitis in a setting of hyper- and hypo-thyroidism and to analyze the correlative linkages between inflammatory mediators and thyroid hormones. Methods. White male 12-14 weeks old inbred rats (n=48) weighing 180-200 g were employed in the experiment. They were randomly divided into the following groups: Group I - control group, Group II - group with a model of periodontitis, Group III - group with a periodontitis in a setting of hyperthyroidism, and Group IV - group with periodontitis in a setting of hypothyroidism. The presence of tumor-necrosis factor-α (TNF-α) and interleukins IL-1β and IL-10 in the periodontal homogenate supernatant was studied by a solid-phase enzyme-linked immunosorbent assay. Results. It was shown that experimental lipopolysaccharide (LPS)-induced periodontitis is accompanied by hyperproduction of pro-inflammatory cytokines (TNF-α, IL-1β) and reduction of anti-inflammatory cytokines (IL-10), whereas TNF-α underwent to maximum changes. Thyroid dysfunction exacerbates cytokine imbalance and severity of inflammation in experimental LPS-induced periodontitis, especially pronounced at hyperthyroidism, as evidenced by the predominance of TNF-α and IL-1β levels in the periodontal homogenate supernatant by 38.5% (р<0.01) and 75.6% (p<0.001), respectively, hyperthyroid over the euthyroid, and by 20.1% (p<0.05) and 24.1% (p<0.05), respectively, over the hypothyroid rats. Conclusions. Thyroid dysfunction, especially hyperthyroidism, may play an important role in the pro-inflammatory response in periodontitis. Hyperproduction of inflammatory mediators in thyroid dysfunction can induce a noticeable damage in the whole apparatus of the periodontium, thereby causing progression of periodontitis.

Dexmedetomidine post-conditioning attenuates cerebral ischemia following asphyxia cardiac arrest through down-regulation of apoptosis and neuroinflammation in rats

BackgroundNeuroprotection strategies after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) remain key areas of basic and clinical research. This study was designed to investigate the neuroprotective effects of dexmedetomidine following resuscitation and potential mechanisms.MethodsAnesthetized rats underwent 6-min asphyxia-based cardiac arrest and resuscitation, after which the experimental group received a single intravenous dose of dexmedetomidine (25 μg/kg). Neurological outcomes and ataxia were assessed after the return of spontaneous circulation. The serum levels and brain expression of inflammation markers was examined, and apoptotic cells were quantified by TUNEL staining.ResultsNeuroprotection was enhanced by dexmedetomidine post-conditioning after the return of spontaneous circulation. This enhancement was characterized by the promotion of neurological function scores and coordination. In addition, dexmedetomidine post-conditioning attenuated the serum levels of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α at 2 h, as well as interleukin IL-1β at 2, 24, and 48 h. TUNEL staining showed that the number of apoptotic cells in the dexmedetomidine post-conditioning group was significantly reduced compared with the control group. Further western blot analysis indicated that dexmedetomidine markedly reduced the levels of caspase-3 and nuclear factor-kappa B (NF-κB) in the brain.ConclusionsDexmedetomidine post-conditioning had a neuroprotective effect against cerebral injury following asphyxia-induced cardiac arrest. The mechanism was associated with the downregulation of apoptosis and neuroinflammation.

Lanthionine, a Novel Uremic Toxin, in the Vascular Calcification of Chronic Kidney Disease: The Role of Proinflammatory Cytokines.

Vascular calcification (VC) is a risk factor for cardiovascular events and mortality in chronic kidney disease (CKD). Several components influence the occurrence of VC, among which inflammation. A novel uremic toxin, lanthionine, was shown to increase intracellular calcium in endothelial cells and may have a role in VC. A group of CKD patients was selected and divided into patients with a glomerular filtration rate (GFR) of <45 mL/min/1.73 m2 and ≥45 mL/min/1.73 m2. Total Calcium Score (TCS), based on the Agatston score, was assessed as circulating lanthionine and a panel of different cytokines. A hemodialysis patient group was also considered. Lanthionine was elevated in CKD patients, and levels increased significantly in hemodialysis patients with respect to the two CKD groups; in addition, lanthionine increased along with the increase in TCS, starting from one up to three. Interleukin IL-6, IL-8, and Eotaxin were significantly increased in patients with GFR < 45 mL/min/1.73 m2 with respect to those with GFR ≥ 45 mL/min/1.73 m2. IL-1b, IL-7, IL-8, IL-12, Eotaxin, and VEGF increased in calcified patients with respect to the non-calcified. IL-8 and Eotaxin were elevated both in the low GFR group and in the calcified group. We propose that lanthionine, but also IL-8 and Eotaxin, in particular, are a key feature of VC of CKD, with possible marker significance.

Apoptosis and Oxidative Stress Triggered by Carbon Black Nanoparticle in the LA-9 Fibroblast.

A new type of nanoparticle, called NP CB-EDA (Black Carbon modified with ethylenediamine), is commonly used in the oil industry. In the literature, few studies are found in biological models, making NP-EDA potential cytotoxicity in organisms unclear. As its large surface area is capable of interacting with the biological system, that interaction could lead to factors harmful to health. The objective of this study was to investigate the cytotoxic effect of NP CB-EDA on fibroblasts LA-9 at 24 and 48 hours, at different concentrations of the nanoparticle (1, 50, 250, 500 and 1000 µg/ml). NP CB-EDA was characterized by TEM microscopy and its effect on cell viability (MTT method), cell morphology (optical microscopy), cell membrane (lactate dehydrogenase release - LDH), oxidative stress pathways (species levels reactive oxygen, ROS and nitrogen, NOS) and apoptosis/necrosis (flow cytometry) were evaluated. The results show that NP CB-EDA at concentrations of 500 and 1000 µg/ml form clusters. The nanoparticle can be absorbed by cells decreasing cell viability. There was damage to the cell membrane of fibroblasts LA 9, an increase in the production of ROS, NOS and pro-inflammatory interleukins TNF-α and IL-6; it was also observed an increase in % of cells in the state of apoptosis in the two periods analyzed, being this response more significant in 24 hours, and concentrations of 250, 500 and 1000 µg/ml presenting higher cytotoxicity. The data suggest that NP CB-EDA in fibroblasts LA9 presents cytotoxic potential, which is associated with oxidative stress and apoptosis.

Efficacy and safety of dupilumab in complex treatment of patients with severe atopic dermatitis

The increased level of interleukins IL-4 and IL-13 in the area of skin lesions, which are secreted by type 2 T-helpers, eosinophils and other immunocompetent cells, plays a main role in the pathogenesis of AD according to modern concepts. The genetically engineered drug dupilumab selectively binds to the subunit of IL-4Rα receptor complexes for IL-4 and IL-13 and inhibits the signaling function of these cytokines. The drug is approved for the treatment of patients with moderate to severe AD who have indications for systemic therapy, regardless of the use of topical corticosteroids from 6 years age. The efficacy and safety of dupilumab in the treatment of patients with atopic dermatitis has been confirmed by the results of numerous clinical studies. Material and methods.The study included 11 patients with moderate and severe AD at the age from 18 to 48 years. All patients received systemic treatment with dupilumab, topically used methylprednisolone aceponate (two times a day for the first 4 weeks, then a calcineurin inhibitor two times a day until the end of the observation period), emollients (two times a day). The initial dose of dupilumab was 600 mg (two injections of 300 mg at different injection sites), then 300 mg every 2 weeks. Results. After 6 months of complex therapy 73 % of patients achieved IGA 0/1. The SCORAD index decreased by an average of 71.7 % after 6 months. The mean value of the NRS scale decreased by 63.2 %. There were no adverse events reported that would lead to drug withdrawal. Conjunctivitis was noted in 2 (18.2 %) patients. Conclusion. There was a marked decrease in the intensity of the main clinical symptoms (SCORAD), including pruritus (NRS), a significant decrease in the manifestations of anxiety and depression (PROMIS).

Sulfasalazine Microparticles Targeting Macrophages for the Treatment of Inflammatory Diseases Affecting the Synovial Cavity.

Rheumatoid arthritis (RA) is a chronic inflammatory disease with sulfasalazine (SSZ) extensively used for long-term treatment of both juvenile and adult RA. Its use is associated with adverse effects and toxicity due to its non-selective biodistribution. Macrophages play an important role in inflammatory processes. In order to target SSZ to macrophages in this work two microparticulate systems (MPs) are developed: SSZ-loaded PLGA MPs without and with α-tocopherol, with particle sizes lower than 5 μm and encapsulation efficiencies of 81.07 ± 11% and 63.50 ± 6.62%, respectively. Release of SSZ from MPs prepared with α-tocopherol was prolonged for 20 days. In RAW 264.7 cell macrophages MPs prepared with α-tocopherol were captured faster. Cell viability studies confirmed that SSZ-loaded MPs prepared without and with α-tocopherol did not produce cytotoxicity at the concentrations assayed. The anti-inflammatory activity of SSZ-loaded MPs was studied by quantifying interleukins IL-1, IL-6 and TNF-α in macrophages. All formulations produced a significant reduction of cytokine concentrations after 24 and 72 h, indicating that release of SSZ from the MPs was able to inhibit the inflammatory response induced by lipopolysaccharide (LPS). Gene expression of IL-1, IL-6 and TNF-α was decreased by SSZ-loaded MPs. SSZ-loaded MPs prepared with α-tocopherol will potentially allow increasing the residence time of SSZ in the synovial cavity, prolonging its duration of action, and reducing the adverse effects associated with its non-selective biodistribution.

Dynamics of cytokines in osteosis splinter fractures replacement in dogs with hydroxyapatite ceramics silicon-doped

Among the entire public of fractures of long bones, more complications of reparative osteogenesis occur fragmental fractures. Their significant defects, which arise as a result of the removal of non-viable fragments, cause disturbances in local hemodynamics and microcirculation and loss of osteoconduction in the area of injury, lead to a loss of the reparative potential of bone tissue in the defect zone, and the methods of osteosynthesis do not provide restoration of osteoconduction and do not have osteointegration properties. For osteosis, a number of composite materials have been proposed, among which ceramics based on calcium phosphates are considered the most promising, which is confirmed by previous clinical, radiological and histomorphological studies. The aim of the study is to determine the dynamics of the blood levels of TGF-β and interleukins IL-1β and IL-10 for osteosis replacement of splinter bone fractures in dogs with calcium phosphate ceramics doped with silicon. Material and research methods: a control (n = 7) and research group (n = 7) dogs with accidental splinter fractures of long bones were formed. In both groups, extracortical osteosynthesis was performed with a support plate from an unalloyed titanium alloy. In the control group, bone defects were left to heal under a blood clot, and in the experimental group they were replaced with ceramics (GTlKg-3). Blood samples were taken after trauma no later than on the 48th day, and on the third, twelfth, twenty-first, forty-second and 60th days after surgical treatment. The enzyme immunoassay was used to determine the serum levels of interleukins IL-1β and IL-10 and transforming growth factor (TGF-β) тhat for a bureta reaction is a bit of a home-made bottle. The study results showed an anti-inflammatory cytokine profile with physiological norms in dogs. In case of bone injury, it becomes pro-inflammatory in nature, triggers the process of osteoresorption in the fracture area. At the same time, during reparative osteogenesis after extracortical osteosynthesis for splinter fractures, proinflammatory cytokinemia acquires a permanent character with a peak on the forty-second day, and this implies inhibition of metaplasia of cartilaginous regenerate into bone, that is, it slows down the consolidation of the fracture. However, in the case of osteosis with ceramics, the level of pro-inflammatory cytokinemia is significantly lower and continues during the first 12 days with a peak on the third day, during the inflammatory-resorptive stage. However, the key in understanding the effectiveness of osteosis was the dynamics of TGF-β, which showed its biphasic hyperreactivity in control animals, while in experimental animals, its balanced production was noted. Conclusion. Osteosis replacement of bone defects in long tubular bones in dogs with hydroxyapatite with β-tricalcium phosphate ceramics doped with silicon is accompanied by moderate cytokinemia in accordance with the course of the inflammatory-resorptive stage and the phase of remodeling with a peak of induction of transforming growth factor during the period of active osteogenesis forty-second course of reparative osteogenesis.

Immunological Effects of an Add-On Physical Exercise Therapy in Depressed Adolescents and Its Interplay with Depression Severity.

Background: Pro-inflammatory cytokines (PICs) have gained attention in the pathophysiology and treatment of depressive disorders. At the same time, the therapeutic effect of physical activity seems to work via immunomodulatory pathways. The interventional study “Mood Vibes” analyzed the influence of exercise on depression severity (primary endpoint) in depressive adolescents; the influence of PICs on the clinical outcome was analyzed as a secondary endpoint. Methods: Clinically diagnosed depressed adolescents (N = 64; 28.1% male; mean age = 15.9; mean BMI = 24.6) were included and participated either in Whole Body Vibration (WBV) (n = 21) or bicycle ergometer training (n = 20) in addition to treatment-as-usual (TAU). Patients in the control treatment group received TAU only (n = 23). The PICs (interleukin-6—IL-6 and tumor necrosis factor-α—TNF-α) were analyzed before intervention, after 6 weeks of training (t1), and 8 weeks post-intervention (t2). The effects of the treatment on depression severity were rated by self-rating “Depression Inventory for Children and Adolescents” (DIKJ). Results: Basal IL-6 decreased in all groups from t0 to t1, but it increased again in WBV and controls at t2. TNF-α diminished in ergometer and controls from baseline to t1. PIC levels showed no correlation with depression severity at baseline. The influence on DIKJ scores over time was significant for IL-6 in the WBV group (p = 0.008). Sex had an impact on TNF-α (p < 0.001), with higher concentrations in male patients. Higher body mass index was associated with higher IL-6 concentrations over all measurement points (p < 0.001). Conclusions: The positive effects of an intensive add-on exercise therapy on adolescent depression seem to be partly influenced by immunomodulation. A small sample size and non-randomized controls are limitations of this study.

Expression levels of IL-17/IL-23 cytokine-targeting microRNAs 20, 21, 26, 155, and Let-7 in patients with relapsing-remitting multiple sclerosis

ABSTRACT OBJECTIVE: Although multiple sclerosis (MS) is known to be an immune-mediated disease, very little is known about its etiopathogenesis. MicroRNAs (miRNAs) are small non-coding proteins involved in the regulation of gene expression. T-cell activation potential in neurodegenerative diseases has been a research topic of interest in recent years Cytokines play an important role in the course and pathogenesis of MS, The aim of the present study was to analyze expression levels of miR-20, miR-21, miR-26, miR-155, and Let-7, which target the cytokines interleukin IL-17 and IL-23, in order to evaluate the relationship between MS and miRNAs that modulate the expression of cytokines involved in the autoimmune pathway. MATERIALS and METHODS: The study included 20 relapsing-remitting multiple sclerosis (MS) patients who were at least 18 years of age and were undergoing outpatient immunomodulatory therapy and 20 healthy, unrelated individuals who had no systemic disease and were not taking any medication as a control group. Peripheral blood samples were collected from all participants into EDTA-containing tubes and plasma was isolated for cDNA synthesis. From these cDNA samples, miRNA expression levels were quantitatively analyzed via melting curve analysis using the miScript SYBR Green kit in real-time PCR device. RESULTS: Comparison of miRNA expression levels in the peripheral blood samples and MS patients and healthy subjects revealed that the MS patients had significant upregulation of miR-20 and downregulation of miR-26 and miR-155 compared to the control group (p<0.005). CONCLUSION: Dysregulation of miRNA expression may play a role in the pathogenesis of MS.

New peptides with immunomodulatory activity identified from rice proteins through peptidomic and in silico analysis

The new food-derived bio-functional peptides are urgently needed globally, but the separation and purification process for obtaining the immunopeptides from food is low efficiency and highly time-consuming. In the present study, rice proteins were extracted and identified by using liquid chromatography/tandem mass spectrometry (LC-MS/MS). Furthermore, a strategy combining immuno-prediction and in silico simulation was used to screen for peptides showing immunomodulatory activity, including inhibition of the release of nitric oxide, tumor necrosis factor-α, and the interleukins IL-6 and IL-1β in lipopolysaccharide-induced RAW264.7 mouse macrophages. This LC–MS/MS identification and immuno-prediction method may provide insights for the potential identification of more food-derived immunopeptides.

Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can exert antidepressant, anti-inflammatory and neuroprotective properties, but the exact molecular mechanism underlying their effects is still not fully understood. We conducted both in vitro and clinical investigations to test which EPA or DHA metabolites are involved in these anti-inflammatory, neuroprotective and antidepressant effects. In vitro, we used the human hippocampal progenitor cell line HPC0A07/03C, and pre-treated cells with either EPA or DHA, followed by interleukin 1beta (IL1β), IL6 and interferon-alpha (IFN-α). Both EPA and DHA prevented the reduction in neurogenesis and the increase in apoptosis induced by these cytokines; moreover, these effects were mediated by the lipoxygenase (LOX) and cytochrome P450 (CYP450) EPA/DHA metabolites, 5-hydroxyeicosapentaenoic acid (HEPE), 4-hydroxydocosahexaenoic acid (HDHA), 18-HEPE, 20-HDHA, 17(18)-epoxyeicosatetraenoic acid (EpETE) and 19(20)-epoxydocosapentaenoic acid (EpDPA), detected here for the first time in human hippocampal neurones using mass spectrometry lipidomics of the supernatant. In fact, like EPA/DHA, co-treatment with these metabolites prevented cytokines-induced reduction in neurogenesis and apoptosis. Moreover, co-treatment with 17(18)-EpETE and 19(20)-EpDPA and the soluble epoxide hydroxylase (sEH) inhibitor, TPPU (which prevents their conversion into dihydroxyeicosatetraenoic acid (DiHETE)/ dihydroxydocosapentaenoic acid (DiHDPA) metabolites) further enhanced their neurogenic and anti-apoptotic effects. Interestingly, these findings were replicated in a sample of n = 22 patients with a DSM-IV Major Depressive Disorder, randomly assigned to treatment with either EPA (3.0 g/day) or DHA (1.4 g/day) for 12 weeks, with exactly the same LOX and CYP450 lipid metabolites increased in the plasma of these patients following treatment with their precursor, EPA or DHA, and some evidence that higher levels of these metabolites were correlated with less severe depressive symptoms. Overall, our study provides the first evidence for the relevance of LOX- and CYP450-derived EPA/DHA bioactive lipid metabolites as neuroprotective molecular targets for human hippocampal neurogenesis and depression, and highlights the importance of sEH inhibitors as potential therapeutic strategy for patients suffering from depressive symptoms.

Biological drugs in the therapy of atopic dermatitis and bronchial asthma: focus on dupilumab

Significant progress has been made over the past decade in the treatment of allergic diseases such as atopic dermatitis and bronchial asthma. Dupilumab, which targets interleukin IL-4 and IL-13, has become an innovative targeted therapy. Immunobiologic therapy with the interleukin inhibitor is indicated for patients with moderate to severe uncontrolled atopic dermatitis, moderate to severe eosinophilic phenotype of uncontrolled Bronchial asthma and patients with poorly controlled severe chronic polyposis rhinosinusitis. A clinical case and recent data on the use of dupilumab for the treatment of type 2 inflammatory disease and prospects for its use are discussed.

Serum free culture for the expansion and study of type 2 innate lymphoid cells

Type 2 innate lymphoid cells (ILC2s) were discovered approximately ten years ago and their clinical relevance is gaining greater importance. However, their successful isolation from mammalian tissues and in vitro culture and expansion continues to pose challenges. This is partly due to their scarcity compared to other leukocyte populations, but also because our current knowledge of ILC2 biology is incomplete. This study is focused on ST2+ IL-25Rlo lung resident ILC2s and demonstrate for the first time a methodology allowing mouse type 2 innate lymphoid cells to be cultured, and their numbers expanded in serum-free medium supplemented with Interleukins IL-33, IL-2, IL-7 and TSLP. The procedures described methods to isolate ILC2s and support their growth for up to a week while maintaining their phenotype. During this time, they significantly expand from low to high cell concentrations. Furthermore, for the first time, sub-cultures of primary ILC2 purifications in larger 24- and 6-well plates were undertaken in order to compare their growth in other media. In culture, ILC2s had doubling times of 21 h, a growth rate of 0.032 h−1 and could be sub-cultured in early or late phases of exponential growth. These studies form the basis for expanding ILC2 populations that will facilitate the study and potential applications of these rare cells under defined, serum-free conditions.

Serum Analyte Profiles Associated With Crohn's Disease and Disease Location.

Crohn's disease (CD) can affect any segment of the digestive tract but is most often localized in the ileal, ileocolonic, and colorectal regions of the intestines. It is believed that the chronic inflammation in CD is a result of an imbalance between the epithelial barrier, the immune system, and the intestinal microbiota. The aim of the study was to identify circulating markers associated with CD and/or disease location in CD patients. We tested 49 cytokines, chemokines, and growth factors in serum samples from 300 patients with CD and 300 controls. After quality control, analyte levels were tested for association with CD and disease location. We identified 13 analytes that were higher in CD patients relative to healthy controls and that remained significant after conservative Bonferroni correction (P < 0.0015). In particular, CXCL9, CXCL1, and interleukin IL-6 had the greatest effect and were highly significant (P < 5 × 10-7). We also identified 9 analytes that were associated with disease location, with VEGF, IL-12p70, and IL-6 being elevated in patients with colorectal disease (P < 3 × 10-4). Multiple serum analytes are elevated in CD. These implicate the involvement of multiple cell types from the immune, epithelial, and endothelial systems, suggesting that circulating analytes reflect the inflammatory processes that are ongoing within the gut. Moreover, the identification of distinct profiles according to disease location supports the existence of a biological difference between ileal and colonic CD, consistent with previous genetic and clinical observations.

Effects of graded levels of xylo-oligosaccharides on growth performance, serum parameters, intestinal morphology, and intestinal barrier function in weaned piglets.

The objective of this study was to investigate the effects of xylo-oligosaccharides (XOSs) supplementation on growth performance, serum parameters, small intestinal morphology, intestinal mucosal integrity, and immune function in weaned piglets. A total of 240 weaned piglets with an average body weight (BW) of 8.82 ± 0.05 kg (28 d of age) were assigned randomly to four dietary treatments in a 28-d trial, including a control (CON) diet and three diets with XOS supplementation at the concentration of 100 (XOS100), 500 (XOS500), and 1,000 (XOS1000) mg/kg. There were four replicates per treatment with 15 pigs per pen. From day 1 to 14, there were no differences (P > 0.05) in average daily gain (ADG), average daily feed intake, and gain to feed ratio (G:F) during the different treatments. The different doses of XOSs showed a quadratic effect on BW on day 28, ADG, and G:F on day 1 to 28 of piglets (P < 0.05). From day 15 to 28, ADG of pigs fed the XOS500 diet was higher (P < 0.05) than pigs fed the CON diet. During the overall period (day 1 to 28), pigs fed the XOS500 diet had a higher BW, ADG, and G:F than pigs fed the CON diet (P < 0.05). In addition, compared with the CON group, the XOS500 group had significantly higher serum total antioxidant capacity, total superoxide dismutase and catalase levels, and lower malondialdehyde levels on days 14 and 28 (P < 0.05). The serum immunoglobulin G (IgG) concentration in the XOS500 group was also significantly higher compared with the CON group on days 14 and 28 (P < 0.05). However, serum immunoglobulin A and immunoglobulin M were not affected by the dietary treatments. Supplementation of XOS500 to the feed significantly increased the villus height (VH) and VH to crypt depth ratio in the jejunum and ileum in comparison with the CON and XOS1000 groups. Moreover, the XOS500 group significantly elevated the expression levels of occludin and zonula occludens protein-1 in the ileum compared with the CON group. The ileal interleukin (IL)-1β, IL-8, and interferon (IFN)-γ mRNA expression levels in the XOS100 and XOS500 groups were markedly lower than in the CON group. In contrast, the ileal IL-10 mRNA expression levels were remarkably higher in the XOS500 than in the CON group. In conclusion, XOSs have a beneficial effect on growth performance by improving serum antioxidant defense system, serum IgG, small intestinal structure, and intestinal barrier function in weaned piglets.

Role of taraxerone isolated from Leucas lavandulifolia, as an immunomodulator

Ethnopharmacological relevanceThe Indian tradition system of medicine enlists a large number of plants for basic health care. Leucas lavandulifolia is mentioned in the ayurvedic medicinal system and also used among the folklores. The plant is used for the treatment of fever, asthma, psoriasis, dermatitis and healing snake bites. The scientific validation of the plant for their traditional use in different immune related disorders are yet to be explored. Aim of the studyThe study aims to isolate immunomodulatory active compound from Leucas lavandulifolia and evaluating its efficiency in immune related disorders. Materials and methodsThe immunomodulatory activity of the phytocompound is evaluated through in vitro and in vivo studies. The compound purification and identification were done by chromatography and LC/Q-TOF respectively. Its immunomodulatory activity was evaluated in cells like PBMC, neutrophils and macrophages by MTT assay and cell cycle analysis. Animal studies were performed on Swiss albino mice. The levels of IL-4 and IL-6 cytokines were also evaluated in both in vitro and in vivo models. ResultsLeucas lavandulifolia stem portion was found to have good modulatory property. An active immunomodulator was isolated from the methanol extract of the plant. LC/Q-TOF data revealed the isolated compound to be taraxerone. In PBMC, the compound was capable of suppressing the proliferation rate of the compound indicated by a decrease in cell numbers. The activated IL-4 and IL-6 production was also suppressed actively at 25 μg/ml of taraxerone. Similar inhibitory effects were seen in RAW 264.7 and THP-1 macrophage cell lines. An IC50 value of 17.5 μg/ml was obtained for taraxerone in LPS stimulated RAW 264.7 macrophage cell lines. The NO level, IL-4, IL-6 and phagocytosis in the LPS stimulated macrophage was effectively lowered by 25 μg/ml of taraxerone. In PMA stimulated THP-1 Macrophage Cell Lines, taraxerone was capable of suppressing the cell number and IL-6. The compound didn't show any effect on IL-4 levels. The compound exhibited an immunosuppressive activity in PHA induced PMN cells by suppressing the respiratory burst and interleukins IL-4 and IL-6. TX could also suppress the proliferation of DNCB induced monocyte cells and IL-4. The haematological parameters exhibited a significant suppression for the high dose group of taraxerone. The antibody titre and phagocytic index was suppressed by the high dose group, whereas the low dose group did not have any effect. So taraxerone at 50 mg/kg body weight is capable of modulating the B-lymphocytes and macrophages. But the compound has exhibited insignificant effect on the DTH hypersensitivity response and organ index. ConclusionTaraxerone at high concentration was capable of suppressing stimulated PBMC, macrophage and PMN. The activated nitric oxide, IL-4, IL-6 production and phagocytosis was also suppressed. The haematological parameters, antibody titre and phagocytic index was also lowered in antigenically challenged mice. The terpenoid taraxerone exhibits a good modulatory effect on the immune system and proves to be a potent drug for the treatment of many allergic disorders.