Anti-inflammatory Interleukin-10 Research Articles

Evaluation of IL-10, IFN-γ, and thiol-disulfide homeostasis in patients with drug-resistant epilepsy.

This study compared dynamic thiol-disulfide homeostasis (an oxidative stress marker), anti-inflammatory interleukin-10 (IL-10) levels, and proinflammatory interferon gamma (IFN-γ) levels in drug-resistant epilepsy patients with those in patients with well-controlled epilepsy and healthy controls. This prospective cross-sectional study enrolled 89 people: 27 with drug-resistant epilepsy, 30 with well-controlled epilepsy, and 32 healthy controls matched in demographic characteristics. The mean serum IL-10 levels were significantly lower and the mean serum IFN-γ levels significantly higher in the drug-resistant epilepsy patients compared to the well-controlled epilepsy and healthy control groups. The mean serum native thiol (SH) and total thiol (TT) levels were significantly lower, and the disulfide (SS) levels were significantly higher in the drug-resistant group than in the other two groups. The significant differences in thiol-disulfide homeostasis and IL-10 and IFN-γ levels in the drug-resistant epilepsy group suggest that these markers indicate a poor prognosis in epilepsy.

Correlation of the expression of tumor necrosis factor-alpha in chronic periapical lesions with the expression of bacterial chaperonin 60

Background/Aim. Chronic microbial infections of the root canal are a common issue. This process very often causes an immune reaction in the root canal system that results in forming of chronic periapical lesions (PLs). The aim of this study was to determine the quantitative expression of the bacterial heat shock protein (HSP), chaperonin 60 (cpn60), and the pro-inflammatory and anti-inflammatory cytokines in periapical tissue obtained from individuals with chronic PLs and to determine if there is a correlation between the expression of the bacterial HSP and the expression of these cytokines. Methods. The study was performed on 18 PLs and 6 control samples of healthy periapical tissue, taken at the Department of Dentistry, Faculty of Medicine, University of Pristina/Kosovska Mitrovica. The levels of messenger ribonucleic acid (mRNA) expression of pro- and anti-inflammatory cytokines and bacterial HSP were determined by quantitative real-time polymerase chain reaction (RT-PCR) and quantified by comparing to the internal control gene for glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Results. Analysis revealed significantly higher mRNA levels of tumor necrosis factor-alpha (TNF-a) and cpn60 in the tissue of PLs compared with normal periapical tissue (p < 0.05). Contrary to these results, the mRNA expression of anti-inflammatory interleukin-10 (IL-10) was significantly higher in the samples of normal periapical tissue compared with the mRNA levels of this cytokine in the tissue of PLs (p < 0.001). Expression of cpn60 is in strong correlation with TNF-a expression in PLs. Conclusion. cpn60 released from bacteria in periapical tissue could be a strong stimulator of inflammatory response and one of the important players in the pathogenesis of PLs.

Increased Local Inflammatory Response to MOC31PE Immunotoxin After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

BackgroundDespite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), most patients with resectable peritoneal metastases from colorectal cancer experience disease relapse. MOC31PE immunotoxin is being explored as a novel treatment option for these patients. MOC31PE targets the cancer-associated epithelial cell adhesion molecule, and kills cancer cells by distinct mechanisms, simultaneously causing immune activation by induction of immunogenic cell death (ICD).MethodsSystemic and local cytokine responses were analyzed in serum and intraperitoneal fluid samples collected the first three postoperative days from clinically comparable patients undergoing CRS-HIPEC with (n = 12) or without (n = 26) intraperitoneal instillation of MOC31PE. A broad panel of 27 pro- and antiinflammatory interleukins, chemokines, interferons, and growth factors was analyzed using multiplex technology.ResultsThe time course and magnitude of the systemic and local postoperative cytokine response after CRS-HIPEC were highly compartmentalized, with modest systemic responses contrasting substantial intraperitoneal responses. Administration of MOC31PE resulted in changes that were broader and of higher magnitude compared with CRS-HIPEC alone. Significantly increased levels of innate proinflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF) as well as an interesting time response curve for the strong T-cell stimulator interferon (IFN)-γ and its associated chemokine interferon gamma-induced protein/chemokine (C-X-C motif) ligand 10 (IP-10) were detected, all associated with ICD.ConclusionsOur study revealed a predominately local rather than systemic inflammatory response to CRS-HIPEC, which was strongly enhanced by MOC31PE treatment. The MOC31PE-induced intraperitoneal inflammatory reaction could contribute to improve remnant cancer cell killing, but the mechanisms remain to be elucidated in future studies.

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.

SIRT1-Dependent Upregulation of BDNF in Human Microglia Challenged with Aβ: An Early but Transient Response Rescued by Melatonin.

Microglia represent a first-line defense in the brain. However, in pathological conditions such as Alzheimer’s disease (AD), a pro-inflammatory switch may occur, leading to loss of protective functions. Using the human microglial cell line HMC3, we showed that exposure to low concentrations of β-amyloid peptide 1-42 (Aβ42; 0.2 μM) initially (6 h) upregulated anti-inflammatory markers interleukin (IL)-4, IL-13, and brain-derived neurotrophic factor (BDNF). BDNF increase was prevented by selective inhibition of SIRT1 with EX527 (2 μM). Accordingly, these early effects were accompanied by a significant Aβ42-induced increase of SIRT1 expression, nuclear localization, and activity. SIRT1 modulation involved adenosine monophosphate-regulated kinase (AMPK), which was promptly (30 min) phosphorylated by Aβ42, while the AMPK inhibitor BML-275 (2 μM) attenuated Aβ42-induced SIRT1 increase. Initially observed microglial responses appeared transient, as microglial features changed when exposure to Aβ42 was prolonged (0.2 μM for 72 h). While SIRT1 and BDNF levels were reduced, the expression of inflammatory markers IL-1β and tumor necrosis factor (TNF)-α increased. This coincided with a rise in NF-kB nuclear localization. The effects of melatonin (1 μM) on prolonged microglial exposure to Aβ42 were analyzed for their protective potential. Melatonin was able to prolong SIRT1 and BDNF upregulation, as well as to prevent NF-kB nuclear translocation and acetylation. These effects were sensitive to the melatonin receptor antagonist, luzindole (25 μM). In conclusion, our data define an early microglial defensive response to Aβ42, featuring SIRT1-mediated BDNF upregulation that can be exogenously modulated by melatonin, thus identifying an important target for neuroprotection.

Manganese exacerbated chronic khat-induced neurological deficits, inflammation and organ toxicity in a mouse model

This study sought to determine whether chronic exposure to khat (Catha Edulis, Forsk) increases the vulnerability to the toxic effects of manganese (Mn2+), when co-exposed. Three (3)-week-old forty (40) Swiss albino mice were randomly divided into four groups (n = 10). The various groups received khat and manganese separately or both. The experiment was conducted for 132 days to mimic chronic exposure to khat, with manganese administration in the last twelve days. Khat-induced neurological deficits were markedly pronounced on co-exposure with manganese. Notably, deficits in motor performance, touch escape and aggression were deepened by manganese. Co-exposure (khat + Mn2+) induced more profound changes in hematological indices such as suppression of RBCs, low hematocrit and hemoglobin levels. Manganese enhanced khat-induced depletion of a very powerful antioxidant, glutathione (GSH) in the brain, liver, heart and lung tissues. Exposure to khat and/or manganese led to significant elevations in the pro-inflammatory cytokines—tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-ϒ), with a concomitant suppression of the anti-inflammatory cytokine and interleukin 10 (IL-10). Similarly, there was enhanced suppression of IL-10 following co-exposure (khat + Mn). Khat-induced hepatotoxicity and nephrotoxicity were exacerbated by co-exposure. In conclusion, acute exposure to manganese appears to aggravate neurological deficits and other multiple organ toxicities driven by chronic exposure to khat.

Regular Exercise May Restore Certain Age-Related Alterations of Adaptive Immunity and Rebalance Immune Regulation.

Age-related changes of the immune system lead to an increased morbidity and mortality due to enhanced vulnerability to infectious diseases and malignancies. Recent studies revealed the important effects of physical activity on immune functions, which may largely depend on the type of exercise, its intensity and duration. However, limited information is available regarding the immunological effects of sport activities in older ages. The aim of our study was to examine the changes in a wide spectrum of lymphocyte subtypes after regular workout among healthy elderly individuals. We enrolled 29 elderly women with sedentary lifestyle (mean age: 67.03 ± 3.74 years) to take part in a 6-week long functional conditioning gymnastic exercise program. The percentages of peripheral natural killer (NK), NKT cells, T and B lymphocyte subtypes (early-/late-activated T, naïve and memory T, cytotoxic T (Tc), T-helper (Th)1, Th2, Th17, T regulatory type 1 (Tr1), CD4+CD127lo/-CD25bright Treg, as well as naïve and memory B cells) were determined by flow cytometry. Evaluation of the changes in functional capability of Treg cells was based on in vitro functional assays. At the end of exercise program, in parallel with improvements in body composition and physical performance, significant changes in naïve and memory lymphocyte ratios were observed. Importantly, levels of naïve Tc cells elevated, ratios of effector memory Tc cells decreased and distribution of memory B cells rearranged as well. Additionally, proportions of late-activated HLA-DR+ T cells increased, while percentages of anti-inflammatory interleukin (IL)-10 producing Tr1 cells, as well as immunosuppressive CD4+CD127lo/-CD25bright Treg cells decreased following the exercise workout. Changes observed after the regular exercise program indicate an improvement in the age-related redistribution of certain naïve and memory cell proportions and a retuned immune regulation in older ages.

Features Local Interlacing Status of Elderly Patients with Primary Angle-Closure Glaucoma

An increased share of the elderly in the structure of modern society, along with other causes and risk factors, is accompanied by the growing the incidence of glaucoma. According to international research in the world by 2020 it is predicted that glaucoma patients will increase to 80 million. Among the elderly, glaucoma is a common pathology, the development of which is associated with local disorders of the interleukin profile. However, the features of the latter in patients with primary closed-angle glaucoma in the elderly have not been studied. The purpose of this work is to identify the features and informativeness of local interleukin profile indicators in elderly patients with primary angle — closure glaucoma. The study included 58 patients with primary angle-closure glaucoma of stage II, who made up the main group, aged 60–74 years with a median of 70.1 ± 2.5 years. All patients underwent a comprehensive ophthalmological examination. The diagnosis of primary angle-closure glaucoma was established in accordance with the requirements of the National glaucoma guidelines. The control group consisted of 27 elderly people aged 60 to 74 years with a median of 68.7 ± 2.1 years without signs and manifestations of primary angle-closure glaucoma, who also underwent a comprehensive ophthalmological examination. Changes in proinflammatory interleukins at the local level in the development of primary angle-closure glaucoma are accompanied by a significant increase in their content in all cases. On the contrary, changes in anti-inflammatory interleukins in the lacrimal fluid in patients with the considered ophthalmological pathology are characterized by a significant inhibition of their production. IL-10 are characterized by the most significant decrease at the local level and it is less related to IL-4. Local interlacing profile of patients with primary angle-closure glaucoma elderly are characterized by increased level in the tear fluid of anti-inflammatory IL-2, IL-17, IL-8 and lower production of anti-inflammatory IL-10. These local interleukins have the greatest informative value, which is of scientific and practical significance for identifying new mechanisms of development, diagnostics and justification of selective immunotropic therapy of the pathology in question.

The Role of Thymoquinone in Mitigating Carbon Tetrachloride-Induced Hepatocellular Carcinoma in Rats: Targeting the CHOP-1/JNK/P38 MAPK, NFκB/TNF-α/IL-10, and Bax/Bcl-2/Caspase-3 Signalling Pathways

The present study was conducted to evaluate the effect of thymoquinone (TQ) on hepatocellular carcinoma (HCC) in rats. Our study has reported that TQ treatment of experimentally-induced HCC results in the up-regulation of the Jun-N-terminal kinase and p38 mitogen activated protein kinase pathway (JNK/p38 MAPK) and the enhancement of anti-inflammatory, anti-oxidant, and pro-apoptotic machineries. TQ resulted in a significant decrease in the levels of nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB), tumor necrosis factor-α (TNF-α), and a significant increase in the anti-inflammatory interleukin-10 (IL-10). The pro-apoptotic effect of TQ was demonstrated through stimulating the apoptotic Bcl-2-associated X (Bax) gene and inhibiting the anti-apoptotic B-cell lymphoma 2 (Bcl-2) gene together with increasing the level of caspase 3 and up-regulating the C/EBP homologous protein (CHOP-1) gene expression. TQ treatment also enhanced the activity of the ROS scavenger, superoxide dismutase (SOD), and decreased the level of the lipid peroxidation product malondialdehyde (MDA). TQ-dependent suppression of HCC was associated with the up-regulation of JNK/p38 MAPK, enhanced CHOP-1 expression, and subsequently increased Bax gene expression.

Cannabidiol-Driven Alterations to Inflammatory Protein Landscape of Lipopolysaccharide-Activated Macrophages In Vitro May Be Mediated by Autophagy and Oxidative Stress.

Background: The nonpsychotropic phytocannabinoid cannabidiol (CBD) presents itself as a potentially safe and effective anti-inflammatory treatment relative to clinical standards. In this present study, we compare the capacity of CBD to the corticosteroid dexamethasone (Dex) in altering the secreted protein landscape of activated macrophages and speculate upon the mechanism underpinning these alterations. Materials and Methods: Human THP-1 monocytes were differentiated into macrophages (THP-1 derived macrophages [tMACs]), activated with lipopolysaccharide (LPS), and then treated with 5, 10, 25, 50, or 100 μM CBD or 10 μM Dex for 24 h. Following treatment, cytotoxicity of CBD and protein expression levels from culture supernatants and from whole cell lysates were assessed for secreted and intracellular proteins, respectively. Results: High concentration (50 and 100 μM) CBD treatments exhibit a cytotoxic effect on LPS-activated tMACs following the 24-h treatment. Relative to the LPS-activated and untreated control (M[LPS]), both 25 μM CBD and 10 μM Dex reduced expression of pro-inflammatory markers-tumor necrosis factor alpha, interleukin 1 beta, and regulated on activation, normal T cell expressed and secreted (RANTES)-as well as the pleiotropic marker interleukin-6 (IL-6). A similar trend was observed for anti-inflammatory markers interleukin-10 and vascular endothelial growth factor (VEGF). Dex further reduced secreted levels of monocyte chemoattractant protein-1 in addition to suppressing IL-6 and VEGF beyond treatments with CBD. The anti-inflammatory capacity of 25 μM CBD was concurrent with reduction in levels of phosphorylated mammalian target of rapamycin Ser 2448, endothelial nitric oxide synthase, and induction of cyclooxygenase 2 relative to M(LPS). This could suggest that the observed effects on macrophage immune profile may be conferred through inhibition of mammalian target of rapamycin complex 1 and ensuing induction of autophagy. Conclusion: Cumulatively, these data demonstrate cytotoxicity of high concentration CBD treatment. The data reported herein largely agree with other literature demonstrating the anti-inflammatory effects of CBD. However, there is discrepancy within literature surrounding efficacious concentrations and effects of CBD on specific secreted proteins. These data expand upon previous work investigating the effects of CBD on inflammatory protein expression in macrophages, as well as provide insight into the mechanism by which these effects are conferred.

Nicotinamide Adenine Dinucleotide (NAD+) Improves Lung Function in Rat Lung Ex-Vivo Lung Perfusion Model

Purpose Ischemia-reperfusion injury compromises short- and long-term outcome after lung transplantation. The scarce existing data on the natural co-enzyme NAD+ suggest an antagonistic effect on hypoxia induced vasoconstriction, removal capacity on reactive oxygen species, and anti-inflammatory effects. We therefore investigated the impact of NAD+ on ischemic rat lungs during ex-vivo lung perfusion (EVLP). Methods Lungs were retrieved from 12 outbred Sprague Dawley male rats and exposed to 14 hours of cold ischemic storage. All lungs were then perfused in a rat EVLP system for 4 hours. Lung grafts were injected after 1, 2 and 3 hours with 2000 uM NAD+ (N=6) or placebo (N=6) in the perfusate in proximity of the pulmonary artery. EVLP physiology and biochemistry were monitored. Results During the 4 hours of EVLP, the lung function increased significantly in the NAD+ group when compared to the placebo group. We monitored a higher vascular flow (p=0.018), a lower mean pulmonary pressure (p=0.007) and increased oxygenation capacity (p=0.003). Lung compliance and weight were comparable. Tissue inflammation measured by myeloperoxidase was significantly lower in the NAD+ group (p=0.015). In the perfusate, we observed in the NAD+ group significantly lower levels of pro-inflammatory interleukin-18 (p=0.033) and a trend towards high levels of anti-inflammatory interleukin-10 (p=0.080) and low levels of pro-inflammatory interleukin-12 (p=0.146). Conclusion Findings from this preliminary study demonstrated that NAD+ is a promising agent with both anti-inflammatory properties and the ability to improve ischemic lung function. This observation should be validated in a large animal model.

ABCB5+ dermal mesenchymal stromal cells with favorable skin homing and local immunomodulation for recessive dystrophic epidermolysis bullosa treatment.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, incurable blistering skin disease caused by biallelic mutations in type VII collagen (C7). Advancements in treatment of RDEB have come from harnessing the immunomodulatory potential of mesenchymal stem cells (MSCs). Although human bone marrow-derived MSC (BM-MSC) trials in RDEB demonstrate improvement in clinical severity, the mechanisms of MSC migration to and persistence in injured skin and their contributions to wound healing are not completely understood. A unique subset of MSCs expressing ATP-binding cassette subfamily member 5 (ABCB5) resides in the reticular dermis and exhibits similar immunomodulatory characteristics to BM-MSCs. Our work aimed to test the hypothesis that skin-derived ABCB5+ dermal MSCs (DSCs) possess superior skin homing ability compared to BM-MSCs in immunodeficient NOD-scid IL2rgammanull (NSG) mice. Compared to BM-MSCs, peripherally injected ABCB5+ DSCs demonstrated superior homing and engraftment of wounds. Furthermore, ABCB5+ DSCs vs BM-MSCs cocultured with macrophages induced less anti-inflammatory interleukin-1 receptor antagonist (IL-1RA) production. RNA sequencing of ABCB5+ DSCs compared to BM-MSCs showed unique expression of major histocompatibility complex class II and Homeobox (Hox) genes, specifically HOXA3. Critical to inducing migration of endothelial and epithelial cells for wound repair, increased expression of HOXA3 may explain superior skin homing properties of ABCB5+ DSCs. Further discernment of the immunomodulatory mechanisms among MSC populations could have broader regenerative medicine implications beyond RDEB treatment.

Surface characterization and biological assessment of corrosion-resistant a-C:H:SiOx PACVD coating for Ti-6Al-4V alloy

The paper focuses on the SiOx-doped amorphous hydrocarbon (a-C:H:SiOx) coating on the titanium (Ti-6Al-4V) alloy substrate obtained by plasma-assisted chemical vapor deposition (PACVD) in a mixture of argon gas and polyphenylmethylsiloxane vapor using a bipolar substrate bias. It is shown that the a-C:H:SiOx coating deposition results in the formation of a negative surface potential important for application of this coating for medical implants. The a-C:H:SiOx coatings improve the corrosion resistance of Ti alloy to 0.5 M NaCl solution and phosphate-buffered saline. In particular, the corrosion current density of the a-C:H:SiOx-coated sample in a 0.5 M NaCl solution at 22 °C decreases from 1∙10−8 to 1.7∙10−10 A/cm2, that reduces the corrosion rate from 9∙10−5 to 15∙10−7 mm/year. The a-C:H:SiOx coating facilitates the surface endothelization of an implant located in the thoracic aorta of a mini pig, and reduces the risk of thrombosis and implant failure. This effect can be explained by the ability of the a-C:H:SiOx coating ability to reduce in vitro a 24-hour secretion of pro-inflammatory interleukins (IL-6, IL-12(p70), IL-15, and IL-17) and cytokines (IFN-g and TNF-a) by blood mononuclear cells (MNCs) and elevates the concentration of anti-inflammatory interleukin IL-1Ra. In vitro analysis shows no cytotoxicity of the a-C:H:SiOx coating for the human blood MNCs, suggesting a promising PACVD on Ti alloys for cardiovascular implants, including pumps for mechanical heart support systems.

Interleukin-10: A double-edged sword in breast cancer.

Breast cancer (BC) is a frequently diagnosed cancer among women worldwide. Currently, BC can be divided into different subgroups according to the presence of the following hormone receptors: estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Each of these subgroups has different treatment strategies. However, the presence of new metastatic lesions and patient deterioration suggest resistance to a given treatment. Various lines of evidence had shown that cytokines are one of the important mediators of tumor growth, invasion, metastasis, and treatment resistance. Interleukin-10 (IL-10) is an immunoregulatory cytokine, and acts as a poor prognostic marker in many cancers. The anti-inflammatory IL-10 blocks certain effects of inflammatory cytokines. It also antagonizes the co-stimulatory molecules on the antigen-presenting cells. Here, we review the current knowledge on the function and molecular mechanism of IL-10, and recent findings on how IL-10 contributes to the progression of BC.

Prolonged Peripheral Immunosuppressive Responses as Consequences of Random Amphetamine Treatment, Amphetamine Withdrawal and Subsequent Amphetamine Challenges in Rats

Drug-induced immunosuppression may underline increased hypothalamic–pituitary–adrenal axis response to stress observed following chronic psychostimulant treatment. However, the consequences of random amphetamine (AMPH) treatment, withdrawal and AMPH challenge after withdrawal on the peripheral immunity and systemic corticosterone response are unknown. In this study, the total blood and spleen leukocyte, lymphocyte, T, B, NK, TCD4+/TCD8+ cell numbers and ratio, pro-inflammatory interferon gamma (IFN-γ), and anti-inflammatory interleukin-4 (IL-4) production, and plasma corticosterone concentration in Wistar rats were investigated after: chronic, random AMPH/SAL treatment alone (20 injections in 60 days, 1 mg/kg b.w., i.p.), AMPH/SAL withdrawal (for 20 consecutive days after random AMPH/SAL exposure) or AMPH/SAL challenge after withdrawal (single injection after the AMPH/SAL withdrawal phase). The results showed blood and spleen leukopenia, lymphopenia, lower blood production of IFN-ɤ, and increased plasma corticosterone concentration after the AMPH treatment, which were more pronounced in the AMPH after withdrawal group. In contrast, an increased number of blood NK cells and production of IL-4 after chronic, random AMPH treatment alone, were found. Blood AMPH-induced leukopenia and lymphopenia were due to decreased total number of T, B lymphocytes and, at least in part, of granulocytes and monocytes. Moreover, decreases in the number of blood TCD4+ and TCD8+ lymphocytes both in the AMPH chronic alone and withdrawal phases, were found.The major findings of this study are that AMPH treatment after the long-term withdrawal from previous random AMPH exposure, accelerates the drug-induced immunosuppressive and systemic corticosterone responses, suggesting prolonged immunosuppressive effects and an increase in incidence of infectious diseases.Graphical Prolonged peripheral immunosuppressive responses as consequences of random amphetamine…The results indicate that the chronic and random AMPH exposure alone and the acute (single injection) challenge of the drug after the withdrawal phase induced long-term immunosuppressive effects, which were similar to those occurring during the stress response, and sensitized the peripheral immunosuppressive and corticosterone responses of the rat to the disinhibitory effects of this stressor.

Inhibition of anti-inflammatory cytokines, IL-10 and TGF-β, in Leishmania major infected macrophage by miRNAs: A new therapeutic modality against leishmaniasis

Leishmania major (L. major) applies several mechanisms to escape the immune system. Interleukin-10 (IL-10) and Transforming Growth Factor (TGF-β) downregulate nitric oxide synthase (iNOS) leading to the survival of Leishmania within macrophages. The miRNAs are known as the modulators of the immune system. The present study was conducted to assess the effect of synthetic miR-340 mimic on cytokines (IL-10 and TGF-β1) involved in L. major infected macrophages. The miRNAs targeting of IL-10 and TGF-β1 was predicted using bioinformatic tools. Relative expression of predicted miRNA, IL-10, and TGF-β1 was measured by RT-qPCR before and after synthetic miRNA mimic transfection. Concentration of IL-10 and TGF-β was measured in posttreatment condition using ELISA method. Also, infectivity was assessed by Giemsa staining. mmu-miR-340 received the highest score for targeting cytokines. The expression of miR-340 was downregulated in L. major infected macrophages. By contrast, expression of IL-10 and TGF-β1 was upregulated in infected macrophages. After miRNA transfection, TGF-β1 and IL-10 were both downregulated and interestingly, the combination of miR-340 and miR-27a had a stronger effect on the downregulation of target genes. This research revealed that transfection of infected macrophages with miR-340 alone or in combination with miR-27a mimic can reduce macrophage infectivity and might be introduced as a novel therapeutic agent for cutaneous leishmaniasis.

Regional anesthesiological support for the implementation of surgical interventions in the abdomen of dogs

Widespread use of surgical interventions in the abdomen of dogs determines the relevance of the study. The research tested the influence of therapeutic epidural blockade with 0.2% bupivacaine after surgical interventions on the background of potentiated local anaesthesia on the body of clinically healthy dogs undergoing ovariohysterectomy. In the control group postoperative analgesia was performed with the nonsteroidal anti-inflammatory drug rimadyl on the background of potentiated thiopental anaesthesia. Wound healing rates were determined in 10 animals of both control and experimental groups; blood counts and the level of inflammatory response were indicated in 5 animals of each group. The dynamics of reparative processes and complete wound healing in dogs of the experimental group occurred earlier than in animals of the control group, which confirmed the fact that the use of bupivacaine had a beneficial effect on tissue regeneration. The results of morphological and biochemical parameters of blood in animals of the experimental group manifested only an increase of leukocytes by 1.58 times, fibrinogen by 2.02 times, while in dogs of the control group the level of erythrocytes, haemoglobin and hematocrit decreased, leukocytes increased by 1.74 times, platelets decreased by 2.87 times and fibrinogen increased by 1.72 times. Among the stress response markers in the control group there was a 1.94 times increase in glucose level after surgery. In the experimental group there was a decrease in the intensity of the inflammatory reaction in dogs, accompanied by an increase of anti-inflammatory interleukin 4 (IL-4) only on the seventh day – 1.86 times, while in the control group the level of anti-inflammatory interleukin 1 receptor antagonist (IL-1RA) after three days increased by 2.30 times, after seven days – by 2.48 times, and the level of proinflammatory interleukin 6 (IL-6) after surgery increased by 2.57 times. It will be promising to conduct further research on the influence of therapeutic blockades with bupivacaine in animals in cases of various surgical interventions and pathological conditions, which will lead to faster recovery of animals and alleviate pathological processes.

Occupational exposure of rural workers to pesticides in a vegetable-producing region in Brazil.

The health of family farmers is at risk due to occupational exposure to pesticides. The aims of the current study were to investigate the level of farmers' perception of risks associated with pesticide use and to assess their health condition based on biochemical and immunological tests. Family farmers living in a vegetable-producing region in Southern Brazil were selected to participate in the study. More than 70% of the family farmers were often exposed to more than one type of pesticides; 41.2% were intensively using several pesticides for more than one decade and 74.4% were not using personal protective equipment (PPE) at the time of pesticide handling due to low perception of the risks posed by these chemicals. Enzymatic analysis performed in participants' blood samples showed changes in catalase (CAT) and glutathione reductase (GR) activity, in lipid peroxidation (TBARS) and carbonylated protein levels, as well as in chemoattractant (IL-8) and anti-inflammatory (IL-10) interleukin expression. Low perception of health-related risks posed by pesticides can be attributed to factors such as low schooling and lack of information, which put farmers' health at risk, as evidenced by blood biochemical and immunological changes.

Association of Interleukin-10 Gene Polymorphisms with Ulcerative Colitis

This literature review is devoted to the study of the role of polymorphic variants of the anti-inflammatory interleukin-10 gene (Interleukin-10, IL10) in the etiology and pathogenesis of ulcerative colitis in patients of various ethnic groups. Aim . To generalize the results obtained from electronic databases on the study of the characteristics of the course of ulcerative colitis in patients of different ethnic groups, taking into account the carriage of IL10 gene polymorphisms. Materials and methods . Twenty-five studies were selected, including four meta-analyzes devoted to the study of associative relationships of single nucleotide polymorphisms (SNPs) of the IL10 gene isolated from blood samples at positions -592AA/CA, -819CT, -1082АА/GA, and rs3024505 in the development and course of ulcerative colitis. Results. A number of researchers from Europe, Saudi Arabia report an increased incidence of ulcerative colitis among carriers of the IL10-1082AA SNP and a low incidence among carriers of -592AA. Positive associations of IL10-819CT with the prevalence of ulcerative colitis are presented in single reports from Europe, the Middle East and in a number of studies from Asian countries. However, the identified associations, even within the same population, are often contradictory. Perhaps the discrepancies are due to the ethnic heterogeneity of the groups in the considered cohorts, and therefore it is necessary to continue epidemiological studies with a large sample size in specific geographic areas.

The expression patterns of IL-1β and IL-10 and their relation to CYP epoxygenases in normal human placenta

IntroductionThe success of pregnancy depends on the regulation of immunological processes in the placenta. Important mediators of an immune response include pro- and anti-inflammatory interleukins which may be regulated by CYP epoxygenases and their metabolites. The relation between interleukins and CYP epoxygenases expression in human placenta has not yet been studied vastly. Material and methodsWe investigated the expression patterns of IL-1β and IL-10 in embryonic (n=8), early foetal (n=16) and term (n=7) human placenta tissue by an immunohistochemical method and evaluated the results by Kruskal-Wallis test. The obtained data was correlated using Spearman’s correlation coefficient to our previously published data of CYP epoxygenases expression in the same samples. To confirm that Hofbauer cells express IL-10 and IL-1β as well as CYP2C8 and IL-10 together, and thus there is a relation between proteins of interests, we used multiplex immunofluorescent staining. ResultsThe expression of IL-1β decreased with gestational age in cytotrophoblast, syncytiotrophoblast, as well as in Hofbauer cells whilst IL-10 decreased in cytotrophoblast, remained at the same levels in syncytiotrophoblast and increased in Hofbauer cells. In trophoblast cells, we found a statistically significant positive correlation between the expression of CYP2J2 and CYP2C9 with IL-1β, whereas there was no relation between IL-10 and any of the tested CYP epoxygenases. In Hofbauer cells, we found a significant positive correlation between CYP2C8 and IL-10 and a significant negative correlation between CYP2C8 and IL-1β. ConclusionOur results showed that the exact role and relation of interleukins and CYP epoxygenases and their metabolites is dependent on their respective cellular context. Because of IL-10, IL-1β, as well as HBCs play a role in various pathological conditions, further investigation of the exact role of CYP epoxygenase, interleukins and their relations is needed.