TNF-α In Patients Research Articles

Study of tumor necrosis factor receptor in the inflammatory bowel disease.

Ulcerative colitis (UC) and Crohn's disease (CD) are part of Inflammatory Bowel Diseases (IBD) and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells. In addition, the main inflammatory mediator is related to the tumor necrosis factor-alpha (TNF-α). TNF-α is a me-diator of the intestinal inflammatory processes, thus being one of the main cytokines involved in the pathogenesis of IBD, however, its levels, when measured, are present in the serum of patients with IBD. In addition, TNF-α plays an important role in promoting inflammation, such as the production of interleukins (IL), for instance IL-1β and IL-6. There are two receptors for TNF as following: The tumor necrosis factor 1 receptor (TNFR1); and the tumor necrosis factor 2 receptor (TNFR2). They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity. The soluble TNF form binds to the TNFR1 receptor with, and its activation results in a signaling cascade effects such as apoptosis, cell proliferation and cytokine secretion. In contrast, the transmembrane TNF form can bind both to TNFR1 and TNFR2. Recent studies have suggested that TNF-α is one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD, since TNF levels are present in the serum of both patients with UC and CD. Intravenous and subcutaneous biologics targeting TNF-α have revolutionized the treatment of IBD, thus becoming the best available agents to induce and maintain IBD remission. The application of antibodies aimed at neutralizing TNF-α in patients with IBD that induce a satisfactory clinical response in up to 60% of patients, and also induced long-term maintenance of disease remission in most patients. It has been suggested that anti-TNF-α agents inactivate the pro-inflammatory cytokine TNF-α by direct neutralization, i.e., resulting in suppression of inflammation. However, anti-TNF-α antibodies perform more complex functions than a simple blockade.

Pro-inflammatory cytokines in patients with low back pain: A comparative study

Introduction and objectivesThere are controversial results regarding the value of serum IL-8 and TNFα in patients with non-specific low back pain.This study aimed to compare pro-inflammatory cytokines between patients with non-specific back pain and pain-free controls. Materials and methodsWe conducted a case–control study including 106 participants: 46 patients with chronic non-specific low back pain (G1) and 60 pain-free controls (G0). The interleukin (IL-)6, IL-8, IL-17, IL-23, IL-22, and Tumor necrosis factor α (TNFα) were measured. We collected demographic and clinical data, including age, gender, low back pain duration and radicular pain. The pain degree was assessed using the Visual Analogic Scale. ResultsThe mean age was 43.17±8.7 years in G1. Radicular pain was found in 37 cases with a Visual Analogic Scale of 3.03±2.5mm. The magnetic resonance imaging was performed in (G1), showing disk herniation and degenerative disk disease in 54.3% (n=25) and 45.7% of cases (n=21), respectively. The IL-8 was higher in G1 (18.84±44.64 versus 4.34±1.23pg/mL, p:0.033). IL-8 levels correlated with TNFα (0.942, p<10–3), IL-6 (0.490, p=0.011) and Visual Analogic ScaleRadicular-pain (r:0.297, p:0.047).IL-17 was higher in patients with restricted lumbar spine mobility (9.64±20.77 versus 1.19±2.54pg/mL, p:0.014). ConclusionsOur results provide evidence that IL-8 and TNFα play a role in low back pain and radicular pain due to disk degeneration or herniation. These findings could potentially be used by future studies to develop new non-specific low back pain therapeutic strategies.

Local Inflammatory Mediators Involved in Neuropathic Pain.

Polyneuropathy (PNP) is a term to describe diseases of the peripheral nervous system, 50% of which present with neuropathic pain. In some types of PNP, pain is restricted to the skin distally in the leg, suggesting a local regulatory process leading to pain. In this study, we proposed a pro-inflammatory pathway mediated by NF-κB that might be involved in the development of pain in patients with painful PNP. To test this hypothesis, we have collected nerve and skin samples from patients with different etiologies and levels of pain. We performed RT-qPCR to analyze the gene expression of the proposed inflammatory pathway components in sural nerve and in distal and proximal skin samples. In sural nerve, we showed a correlation of TLR4 and TNFα to neuropathic pain, and an upregulation of TNFα in patients with severe pain. Patients with an inflammatory PNP also presented a lower expression of TRPV1 and SIRT1. In distal skin, we found a reduced expression of TLR4 and miR-146-5p, in comparison to proximal skin. Our findings thus support our hypothesis of local inflammatory processes involved in pain in PNP, and further show disturbed anti-inflammatory pathways involving TRPV1 and SIRT1 in inflammatory PNP.

The role of regulatory micro-RNAs in inflammatory processes and production of tumor necrosis factor-alpha in patients with rheumatoid arthritis

Background. Micro-RNAs are fundamental agents of post-transcriptional control of gene expression. In recent years many works have appeared on the possible role of micro-RNAs in rheumatoid arthritis (RA). Studies of the role of micro-RNA and the relationship with the synthesis of tumor necrosis factor-α (TNF-α) are very promising for understanding the pathogenesis and treatment of RA and other autoimmune diseases. The purpose of the research was to study the role of regulatory micro-RNAs in inflammatory processes and the possible connection with the production of TNF-α in patients with RA. Materials and methods. 29 patients with active RA and 20 healthy individuals (control) were examined. All subjects were examined for 16 micro-RNAs. The choice of micro-RNA was based on previous studies and theoretical conclusions (according to the miRWalk database). Rheumatoid factor, the level of antibodies to cyclic peptides containing citrulline, C-reactive protein (СRP), levels of TNF-α (serum, spontaneous, and stimulated) were determined in the blood of patients. Results. Statistical analysis demonstrated significant overexpression of miR-221, miR-203, miR-146b, miR-132, miR-21 and miR-17-3p and inhibition of miR-223 synthesis in RA patients. The activation of TNF-α synthesis at rest and the increased production of TNF-α by mononuclear cells after stimulation in RA were shown. Differences in the levels of relative expression of some micro-RNAs between seropositive and seronegative groups of RA patients were found, but only hyperexpression of miR-155 was highly reliable. For the first time, a possible relationship between TNF-α production and miR-29 and miR-155 micro-RNAs, as well as a correlation between miR-16, miR-99b and miR-203 and CRP levels, was revealed. Conclusions. The obtained data on the profile of micro-RNAs in RA makes it possible to distinguish the most “interesting” micro-RNAs for further study of pathogenesis, their role in inflammation, to study the choice of TNF-α inhibitors, and predicting the effectiveness of that treatment.

Instrumental and laboratory diagnostics of early complications in acute pancreatitis

The aim of the study. Assessment of markers of early complications in patients with acute pancreatitis. Materials and methods. Observation was carried out for 151 patients who were in the clinic from 2011 to 2019, with a diagnosis of acute pancreatitis (OP). The average age of patients (47.8±1.5) years. The patients were divided into 2 groups: group I - 78 patients with developing pancreatic pseudocyst (PP) and group II - 73 patients with free fluid accumulations (FFA) of the abdominal cavity. All patients underwent comprehensive examinations, including histology of emerging cysts, clinical and biochemical blood tests, sonography and computed tomography, bacteriological and enzyme immunoassays with assessment of the level of endogenous intoxication, procalcitonin, microbial contamination and cytokines. Results. In comparison with group I patients with developing PP, the observed group II patients with FFA showed a significant increase in the degree of endogenous intoxication. A 3.0-fold increase in the level of procalcitonin in 26.8% of group I patients and in 67.1% of group II patients (p<0.05) with a directly proportional dependence of this indicator on the level of bacterial contamination (r=+0.51; p<0.05) indicated the activation of infection processes in general and, to a greater extent, in group II patients. At the same time, the condition of their last worsened due to the transition of the inflammatory process to the parapancreatic region and into the retroperitoneal space. The high level of proinflammatory cytokines IL-6, TNF-α in patients of group II compared with group I, an imbalance and a decrease in the activity of the anti-inflammatory mediator IL-10 determined a significantly greater (p<0.05) activity of the inflammatory process in patients with SFS, and were associated with an unfavorable prognosis. Conclusion. The formation of a PP is a relatively favorable outcome of acute pancreatitis, accompanied by significantly less pronounced toxemia and infection rate in comparison with patients with free fluid accumulations of the abdominal cavity.

Эффективность и безопасность различных режимов отмены ингибиторов фактора некроза опухоли альфа при длительной ремиссии ювенильного идиопатического артрита без системных проявлений: результаты проспективного простого рандомизированного исследования

Including the tumor necrosis factor TNF inhibitors (TNFi) in the management guidelines for children with juvenile non-systemic juvenile idiopathic arthritis (JIA) has significantly increased the effectiveness of antirheumatic treatment. However, the guidelines of TNFa withdrawal when disease remission is achieved remains unclear. Objective. To study the efficacy and safety of different TNFi withdrawal regimens in patients with juvenile idiopathic arthritis without systemic manifestations due to the achievement of long-term disease remission. Patients and methods: The prospective simple randomized trial included 76 patients with JIA without non-systemic juvenile idiopathic arthritis, with a disease remission duration of ≥24 months, developed under the conditions of treatment with TNFi. Of these, 38.2% are male, the average age is 11.6 years; 67 (88.2%) patients received etanercept (0.8 mg / kg / week. subcutaneously 1 time per week), the rest – adalimumab (24 mg/m2 subcutaneously 1 time in 2 weeks). Depending on the withdrawal regimen, patients were divided into three groups: in the I group, one-time withdrawa was presented, in the II group, the interval between administrations was of two times and the III group was reduced by a dose of two times. The main indicator of the study: preservation of the stage of inactive disease / remission (according to the criteria for remission of C. Wallace) for 6, 12 and 18 months after the withdrawal of TNFi. Results. At the time of withdrawal of TNFi, the average duration of the disease was 7.3 years, the duration of therapy with TNFa was 5 years, remission – was 4.4 years. For 6, 12 and 18 months after the withdrawal of TNFi, the stage of remission persisted in 44 (57.9%), 21 (27.6%) and 18 (23.7%) patients. Exacerbation of disease was registered in 58/76 (76%) patients. Biologic therapy was resumed in 56/58 children, in all cases the stage of inactive disease was reached. Among patients with exacerbation of JIA, 23/56 (41%) continued to receive disease-modifying antirheumatic drugs. Predictors of successful withdrawal of TNFa in patients with non-systemic JIA 6 and 12 months after discontinuation of the biological therapy were the female sex, the absence of HLA B27, antinuclear factor and long-term methotrexate therapy; predictors of exacerbation - increasing in the serum concentration of calprotectin (S-100 protein), the presence of subclinical synovitis according to ultrasound and MRI of the joints and uveitis. Conclusion. After the withdrawal of TNFi, the remission stage for 6 and 12 months persisted more than in half and one third of patients. The withdrawal regimens did not affect the duration of the remission of disease. The resumption of biological therapy in the exacerbation stage of JIA made it possible to reach the remission stage in most patients. Predictors of successful withdrawal of TNFi in patients with non-systemic JIA 6 and 12 months after discontinuation of the biological therapy were the female sex, the absence of HLA B27, antinuclear factor and long-term methotrexate therapy; predictors of exacerbation – increasing in the serum concentration of calprotectin (S-100 protein), the presence of subclinical synovitis according to ultrasound and MRI of the joints and uveitis. The presence of exacerbation predictors makes it impractical the withdrawal of biological therapy due to the high risk of developing an exacerbation of disease. Key words: (TNF)-alpha inhibitors, juvenile idiopathic arthritis, long-term remission, withdrawal predictors, high-sensitivity C-reactive protein (hsCRP), serum calprotectin (S-100 protein)

Retracted: Analysis of Serum Levels of IFN-γ, IL-4, and TNF-α in Patients with Cervicitis Complicated by HPV Infection and Their Clinical Significance.

[This retracts the article DOI: 10.1155/2022/3374655.].

Features of hematological and immune disorders in the combined treatment of breast cancer patients with the risk of development of late radiation damage

Background. Breast cancer (BC) is one of the most common forms of malignant neoplasms among the female population of Ukraine. The widespread use of radiation therapy in the treatment of BC, along with the improvement of treatment efficiency, inevitably leads to an increase in the probability of early and/or late radiation injuries (LRI), which puts before scientists the task of a detailed study of this problem and the search for ways to prevent the development of LRI.The body’s reaction to the development of a malignant neoplasm and to antitumor treatment is largely determined by the state of homeostatic mechanisms, in the regulation of which one of the key roles is played by the immune system. Recently, special attention has been focused on the role of immune inflammatory responses in the pathogenesis of LRI in cancer patients. All of the above determines the urgency of finding a differential approach to immunocorrective therapy as a prevention of the development of LRI. Рurpose – to determine the characteristics of changes in hematological indicators and the subpopulation composition of lymphocytes during immunocorrective therapy as a prevention of the development of LRI in patients with BC. Materials and Methods. 55 patients with BC were examined. The patients were divided into groups: the comparison group (n=13) – patients with BC with the risk of developing LRI who were given standard therapy, the main group (n=15) – patients with BC with the risk of developing LRI who were given immunocorrective therapy against the background of standard treatment. The control group (n=27) consisted of patients with BC without the risk of developing LRI. The groups were comparable in terms of age and disease stage. Results. Immunocorrective therapy increased the number of erythrocytes, hemoglobin level, CD19+-, CD3+CD8+-lymphocytes, NK-cells, CRP, IL-6, IL-2 and TNF-α in patients of the main group. In patients of the comparison group, after treatment, lower levels of erythrocytes, hemoglobin, lymphocytes, the relative number of CD8+-T-lymphocytes, CD19+-B-lymphocytes and higher levels of the relative number of eosinophils, monocytes, neutrophils, cytokine levels, and CRP were found in comparison with the indicators of patients, who underwent immunocorrective treatment. In patients with BC of the main group, immunocorrection reduces systemic changes that can contribute to the development of late radiation damage and recurrence of the oncological process. The inclusion of immunocorrective therapy with the use of melatonin had a positive effect on the hematological and immune indicators of patients. Conclusions. Immunocorrective therapy in patients at risk of developing LRI optimized immune and hematological parameters: it contributed to an increase in the number of erythrocytes by 1.25 times, hemoglobin level by 1.6 times, CD19+- (1.5 times), CD3+CD8+-lymphocytes (1.1 times), and a decrease in NK cells (1.77 times), CRP by 2.19 times, IL-6 by 1.8 times, IL-2 by 2.13 times, and TNF-α by 3 times, 22 times. It was found that in patients with BC with the possibility of developing LRIwithout immunotherapy, lower levels of erythrocytes (by 1.15 times), hemoglobin (by 1.13 times), lymphocytes (by 1.3 times), and the relative number of CD8+ were observed after treatment - T lymphocytes (1.4 times), CD19+ B lymphocytes (6.5 times) and higher levels of relative numbers of eosinophils, monocytes, neutrophils, cytokine levels (1.5 times) and CRP (2.1 times) in comparison with the indicators of patients who underwent immunocorrective treatment. The appointment of immunocorrective therapy with melatonin in a daily dose of 9 mg during radiation treatment for patients with BC with the risk of developing LRI led to the normalization of hematoimmune indicators, a significant decrease in the systemic inflammatory reaction.

Dark chocolate (70% cocoa) attenuates the inflammatory marker TNF-α in patients on hemodialysis

Inflammation and oxidative stress lead to a high risk of cardiovascular disease in patients with chronic kidney disease (CKD). Food rich in polyphenols such as dark chocolate may be an effective strategy to mitigate inflammation and delay CKD complications, outwith sensorial pleasure promotion. The aim of this study was to evaluate the effects of dark chocolate on inflammation and oxidative stress markers in patients with CKD on hemodialysis (HD). A clinical trial was carried out with 59 patients who were allocated into the chocolate group [40g of dark chocolate (70% cocoa) offered during HD sessions, 3×/week] or the control group with any intervention for two months. Plasma levels of the inflammatory cytokines TNF-α and IL-6 were evaluated by the ELISA method. Thiobarbituric acid reactive substances such as malondialdehyde (MDA) and LDLox levels were evaluated as lipid peroxidation markers. Routine biochemical parameters were analysed using commercial BioClin® kits. Thirty-five patients completed the chocolate group (18 men, 53.0 (16)years and31.0 (39) months on HD) and 11 in the control group (7 men, 48.0 (17.5) years and 44.0 (56.5) months on HD). Regarding the differences between the groups, the patients who received dark chocolate had reduced plasma levels of TNF-α compared to the control (p=0.008). No significant changes were observed in the oxidative stress parameters evaluated in both groups. Routine biochemical (including phosphorus and potassium levels) and anthropometric parameters and food intake were not changed after the study period. The intervention with dark chocolate (70% cocoa) for two months reduced the plasma levels of TNF-α in patients with CKD on HD. In addition, it is essential to emphasise that chocolate intake did not increase the plasma levels of phosphorus and potassium in these patients. This study was registered at clinicaltrials.gov as NCT04600258.

Steroid treatment suppresses the CD4+ T-cell response to the third dose of mRNA COVID-19 vaccine in systemic autoimmune rheumatic disease patients

Prolonged steroid treatment has a suppressive effect on the immune system, however, its effect on the cellular response to mRNA vaccine is unknown. Here we assessed the impact of prolonged steroid treatment on the T-cell and humoral response to the SARS-CoV-2 spike (S) peptide following the third dose of the BNT162b2 vaccine in systemic autoimmune rheumatic disease patients. We found that CD4 T-cell response to the S peptide in patients on high-dose long-term steroid treatment showed significantly less S-peptide specific response, compare to low-dose or untreated patients. Remarkably, these results were not reflected in their humoral response, since almost all patients in the cohort had sufficient antibody levels. Moreover, S-peptide activation failed to induce significant mRNA levels of IFNγ and TNFα in patients receiving high-dose steroids. RNA-sequencing datasets analysis implies that steroid treatments' inhibitory effect of nuclear factor kappa-B signaling may interfere with the activation of S-specific CD4 T-cells. This reveals that high-dose steroid treatment inhibits T-cell response to the mRNA vaccine, despite having sufficient antibody levels. Since T-cell immunity is a crucial factor in the immune response to viruses, our findings highlight the need for enhancing the efficiency of vaccines in immune-suppressive patients, by modulation of the T-cell response.

Selected Mediators of Inflammation in Patients with Acute Ischemic Stroke.

During a stroke, a series of biochemical and metabolic changes occur which eventually lead to the death of cells by necrosis or apoptosis. This is a multi-stage process involving oxidative stress and an inflammatory response from the first signs of occlusion of a blood vessel until the late stages of regeneration and healing of ischemic tissues. The purpose of the research was to assess the concentration of pro-inflammatory cytokines IL-6 and TNF-α in the blood serum of patients with ischemic stroke (AIS) and to investigate their role as new markers in predicting functional prognosis after thrombolytic therapy. The researches have shown that the concentrations of the measured biomarkers were higher compared to the control group. Serum levels of IL-6 and THF-α before the initiation of intravenous thrombolysis were lower in the subgroup of patients with a favourable functional result (mRS: 0–2 pts) compared to the group of patients with an unfavourable functional result (mRS: 3–6 pts). A positive correlation was found between the concentration of IL-6 and TNF-α in patients with AIS during <4.5 h and on one day after the onset of stroke, which means that the concentration of IL-6 increases with the increase in TNF-α concentration. It has also been shown that higher levels of IL-6 in the acute phase of stroke and on the first and seventh days, and TNF-α during onset, were associated with poorer early and late prognosis in patients treated with intravenous thrombolysis. A relationship was found between the level of IL-6 and TNF-α in the subacute AIS and the severity of the neurological deficit. It has been shown that the investigated biomarkers may be a prognostic factor in the treatment of thrombolytic AIS.

Hepatic mir-122-3p, mir-140-5p and mir-148b-5p expressions are correlated with cytokeratin-18 serum levels in MAFLD

Introduction and objectivesMetabolic-associated fatty liver disease (MAFLD) is defined by steatosis in more than 5% of hepatocytes without other liver diseases. Patients with this disease can progress to multiple stages like liver fibrosis, cirrhosis, and hepatocellular carcinoma. miRNAs are single-stranded molecules that regulate metabolic homeostasis; their differential expression postulates them as potential circulating biomarkers for MAFLD. Previous research reported that hsa-miR-140-5p, hsa-miR-148-5p, and hsa-miR-122-3p have a differential expression in patients with MAFLD. This study aimed to investigate the correlation between liver hsa-miR-140-5p, hsa-miR-148-5p, and hsa-miR-122-3p and serum biomarkers CK-18, APOB, IL-6, IL-32, and TNF-α in patients with MAFLD compared with control patients. Materials and methodsA cross-sectional study was carried out with 16 patients of both sexes, aged between 18-60 years, to determine the association between the levels of hsa-miR-140-5p, hsa-miR-148-5p, and hsa-miR-122-3p with MAFLD in liver biopsies of patients who underwent laparoscopic cholecystectomy. ResultsTwelve patients presented MAFLD, four without hepatic steatosis. Circulating levels of CK-18 showed a significant difference in patients with MAFLD, and a strong correlation was found between hsa-miR-122-3p, hsa-miR-140-5p, and hsa-miR-148b-5p versus the CAP value. ConclusionThere is a correlation between elevated tissue expression of hsa-miR-122-3p, hsa-miR-140-5p, and hsa-miR-148b-3p with plasma levels of CK-18 in patients with simple steatosis compared with patients without the disease.

Independent Association of 25[OH]D Level on Reduced Glutathione and TNF-α in Patients ‎with Diabetes and/or Hypertension.

PurposeOxidative and inflammatory pathways play a significant role in the pathophysiology of a wide variety of non-communicable diseases such as type 2 diabetes mellitus (T2DM) and hypertension. However, the effect of serum 25-hydroxyvitamin D ‎‎(25[OH]D) on these pathways is still controversial. To evaluate the association of 25[OH]D on ‎antioxidant and pro-inflammatory biomarkers, reduced glutathione (GSH) and tumor ‎necrosis factor (TNF)-α, in T2DM and hypertensive patients.Patients and MethodsThis is a cross-sectional study of a consecutive sample of patients attending the the Family Medicine clinic at King Abdullah bin Abdulaziz University Hospital (KAAUH). Participants were screened for eligibility according to the following ‎criteria: aged above 18 years and diagnosed with T2DM and/or hypertension for at least one ‎year. Patients receiving any kind of vitamin D or calcium supplements within the last three ‎months were excluded, as were those with a history of ‎renal failure, cancer, liver, thyroid, or any other chronic inflammatory diseases.ResultsIn total 424 T2DM and/or ‎hypertensive patients (mean age 55±12 years) were recruited. In addition to routine ‎physical and laboratory examinations, levels of serum 25[OH]D, GSH and TNF-α were ‎measured. The prevalence of 25[OH]D deficiency (<50 nmol/L) was 35.1%, which was ‎independent from GSH and TNF-α levels. In T2DM, hypertensive and patients having ‎both diseases, GSH levels were 349.3±19, 355.4±19 and 428.8±20 μmol/L, ‎respectively. Uncontrolled T2DM and hypertension patients showed significantly higher ‎GSH compared with the controlled group. ‎Males showed slightly higher level ‎of TNF-α compared with females and uncontrolled hypertensive patients had relatively ‎higher TNF-α level when evaluated against controlled hypertensive patients. ‎Conclusion25[OH]D level is independent of oxidative stress and inflammation, ‎assessed by levels of GSH and TNF-α, respectively, in T2DM and hypertensive Saudi ‎patients. ‎

Efficacy Evaluation of Inflammatory Mediators in the Treatment of Multiple Myeloma with Daratumumab.

Objective This study aimed to investigate the regulatory ability and clinical therapeutic effect of daratumumab on inflammatory mediators in patients with multiple myeloma. Method The Multiple Myeloma Public Genetic Data Array download GSE125361 dataset was collected. The GO analysis and KEGG analysis were performed on the differential genes to elucidate the multiple myeloma cytokine-related gene pathways. Daratumumab is a CD38 monoclonal antibody used to treat multiple myeloma. Patients with newly diagnosed multiple myeloma were treated with monoclonal antibodies containing CD38, and the control group was treated with a regimen without daratumumab. The serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ were measured in the two groups before and after treatment and the therapeutic effects of the two groups were compared. Result The KEGG analysis showed that the Th17 cell differentiation, apoptosis, and cytokine-cytokine receptor interaction pathways were differentially expressed in multiple myeloma. The expression levels of serum IL-2, IL-6, IL-10, and TNF-α in patients in the daratumumab group were lower than those in the control group after chemotherapy. The overall effective rate of patients treated with daratumumab after chemotherapy was higher than that of the control group. Conclusion Daratumumab can effectively improve the levels of IL-2, IL-6, IL-10, and TNF-α in patients with multiple myeloma and improve the therapeutic effect.

&lt;I&gt;TNF-α&lt;/I&gt; gene expression in immune cells of patients with psoriasis and psoriatic arthritis

Introduction. Psoriatic disease is a heterogeneous inflammatory disease with different clinical manifestations, including plaque psoriasis and psoriatic arthritis. It has been shown that elevated levels of TNF-α are observed in both psoriatic arthritis and psoriasis. Studying the TNF-α gene expression pattern can help in the differential diagnosis between psoriatic arthritis and psoriasis.The objective is to study the TNF-α gene expression pattern in blood mononuclear cells of patients with psoriatic arthritis and psoriasis for possible differential diagnosis between these two diseases.Materials and methods. Mononuclear cells were isolated from the peripheral blood of 31 patients with plaque psoriasis, 45 patients with psoriatic arthritis and 20 healthy controls. The expression level of the TNF-α gene was analysed using a real-time PCR method.Results and discussion. As a result of the comparison, the expression level of TNF-α in patients with psoriatic arthritis was found to be 179 times higher than the expression level in healthy volunteers. The expression level of TNF-α in patients with psoriasis was also significantly (106 times) higher than the expression level in healthy people. We managed to identify a significant difference between patients with psoriatic arthritis and psoriasis.Conclusions. Patients with psoriasis in terms of TNF-α gene expression level in mononuclear cells are close to the condition of patients with psoriatic arthritis. A high level of TNF-α gene expression can become a marker of possible joint injury in patients with psoriasis and a signal to revise the therapeutic approach to a particular patient.

Exploring the Relationship between TNF-α Gene Expression in Non Diabetic Nephropathy Type 2 Diabetes Patients

Non-diabetic nephropathy (NDN) is a common complication of type 2 diabetes, leading to kidney damage and impaired kidney function. TNF-α (tumor necrosis factor-alpha) is a pro-inflammatory cytokine that has been implicated in the development of NDN. Objective: To evaluate the gene expression of TNF-α in patients with type 2 diabetes mellitus (T2DM) without nephropathy to gain insight into the potential role of TNF-α in the pathogenesis of diabetic nephropathy (DN). Methods: Total of 80 subjects were tested, split into two groups, including healthy patients, T2DM patients without nephropathy, and T2DM patients with nephropathy. RNA was extracted from blood samples, and RT-PCR was used to observe the impact of T2DM without nephropathy on the expression of the TNF-α gene using gene-specific primers and SYBR Green mix. Results: The results showed almost 4.4-fold induced expression of TNF-α in T2DM patients without nephropathy compared to the normal group. Conclusion: The findings may have implications for the development of new therapies and biomarkers for DN, and for a good interpretation of the complex pathophysiology of T2DM. The exact role of TNF-α in the pathogenesis of DN in humans is not fully understood, and further investigation is needed.

Model Informed Precision Dosing Tool Forecasts Trough Infliximab and Associates with Disease Status and Tumor Necrosis Factor-Alpha Levels of Inflammatory Bowel Diseases.

Background: Substantial inter-and intra-individual variability of Infliximab (IFX) pharmacokinetics necessitates tailored dosing approaches. Here, we evaluated the performances of a Model Informed Precision Dosing (MIPD) Tool in forecasting trough Infliximab (IFX) levels in association with disease status and circulating TNF-α in patients with Inflammatory Bowel Diseases (IBD). Methods: Consented patients undergoing every 8-week maintenance therapy with IFX were enrolled. Midcycle specimens were collected, IFX, antibodies to IFX, albumin were determined and analyzed with weight using nonlinear mixed effect models coupled with Bayesian data assimilation to forecast trough levels. Accuracy of forecasted as compared to observed trough IFX levels were evaluated using Demings’s regression. Association between IFX levels, CRP-based clinical remission and TNF-α levels were analyzed using logistic regression and linear mixed effect models. Results: In 41 patients receiving IFX (median dose = 5.3 mg/Kg), median IFX levels decreased from 13.0 to 3.9 µg/mL from mid to end of cycle time points, respectively. Midcycle IFX levels forecasted trough with Deming’s slope = 0.90 and R2 = 0.87. Observed end cycle and forecasted trough levels above 5 µg/mL associated with CRP-based clinical remission (OR = 7.2 CI95%: 1.7–30.2; OR = 21.0 CI95%: 3.4–127.9, respectively) (p < 0.01). Median TNF-α levels increased from 4.6 to 8.0 pg/mL from mid to end of cycle time points, respectively (p < 0.01). CRP and TNF-α levels associated independently and additively to decreased IFX levels (p < 0.01). Conclusions: These data establish the value of our MIPD tool in forecasting trough IFX levels in patients with IBD. Serum TNF-α and CRP are reflective of inflammatory burden which impacts exposure.

Changes and roles of IL-17A, VEGF-A and TNF-α in patients with cerebral infarction during the acute phase and early stage of recovery

Background and purposeInterleukin 17A (IL-17A), vascular endothelial growth factor A (VEGF-A) and tumour necrosis factor alpha (TNF-α) are important cytokines detected mostly within two weeks after stroke in previous clinical studies. Longer clinical studies investigating these cytokines are lacking. We aimed to explore the roles of these cytokines in patients within 35 days after cerebral infarction. MethodsThirty patients with cerebral infarction and 30 healthy individuals were enrolled. Venous blood was collected from each patient at specific times and from each healthy individual only once. Coma and neurological functional deficits of the patients were evaluated by the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS), respectively. Three cytokines were measured. The correlations among the three cytokines and between each cytokine and the GCS/NIHSS scores were analysed. ResultsIL-17A and TNF-α began to increase on day 1 after cerebral infarction, peaked on day 4, then decreased, and increased again on day 18. IL-17A returned to normal on day 35, but TNF-α remained higher than normal on day 35. VEGF-A began to increase on day 1, peaked on day 7, and returned to normal on day 35. From days 18 to 35, IL-17A was positively correlated with the GCS scores, and both IL-17A and VEGF-A were negatively correlated with the NIHSS scores. ConclusionAfter cerebral infarction, VEGF-A from the acute phase and IL-17A from the early stage of recovery may be important for nerve protection and repair; TNF-α plays a complex role within 35 days.

Evaluation of the Serum Levels of TNF-α and IL-8 in the Patients Undergoing Angiography

Introduction: Angiography is a safe cardiovascular technique for the diagnosis and treatment of cardiovascular disorders. The potential effects of angiography on the levels of cytokines are yet to be clarified completely. Interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) are important pro-inflammatory cytokines that participate in the pathogenesis of artery stenosis. The aim of this study was to investigate the effects of angiography on the serum levels of IL-8 and TNF-α.Methods: Sixty participants in three groups, without, with one, and with more than one artery stenosis, were explored in this project. Serum levels of IL-8 and TNF-α were measured in the participants before and after angiography using the enzyme linked immunosorbent assay (ELISA) technique.Results: Serum levels of IL-8, but not TNF-α, significantly decreased following angiography from 61.45 (9.80-266.72) to 7.00 (3.82-17.85) pg/mL (P = 0.008) in participants without artery stenosis, from 79.40 (7.20-197.40) to 6.80 (3.85-29.50) pg/mL (P = 0.002) in participants with one artery stenosis, and from 91.25 (12.80-145.97) to 10.75 (6.97-49.82) pg/mL (P = 0.004) in participants with more than one artery stenosis. The X-ray dose had a moderate positive correlation with serum levels of TNF-α in patients with more than one artery stenosis (r = 0.584, P = 0.009). Serum levels of IL-8 and TNF-α were not different between male and female participants in none of the groups. Conclusion: Angiography may be a protective factor against inflammation by suppressing IL-8.

MO585: Effects of EPP-AF® Green Propolis Extract Supplementation on Inflammatory Markers in Patients With chronic Kidney Disease on Peritoneal Dialysis

Abstract BACKGROUND AND AIMS Inflammation and oxidative stress are involved in the mortality of patients with chronic kidney disease (CKD) on peritoneal dialysis (PD). In this context, propolis may mitigate inflammation, reducing mRNA expression of nuclear factor-kB (NF-kB) and levels of inflammatory markers as tumor necrosis factor-α (TNF-α). Several studies have been performed in vitro and in animals showing that propolis (a resin made by bees) has excellent anti-inflammatory properties. Only one study evaluated the effects of propolis in patients with CKD (stages 3 and 4) and showed a reduction in proteinuria and urinary MCP-1, but there is no study in patients with CKD on peritoneal dialysis (PD). The present study aimed to evaluate the effects of propolis supplementation on inflammatory markers in patients with CKD on PD. METHODS This is a longitudinal, randomized, double-blind, placebo-controlled trial with 19 patients randomized into two groups: propolis (4 capsules of 500 mg/day containing concentrated and standardized dry EPP-AF® green propolis extract) or placebo (4 capsules of 500 mg/day of magnesium stearate, silicon dioxide and microcrystalline cellulose as placebo) for 2 months. The inflammatory cytokines plasma levels such as TNF-α and interleukin-6 (IL-6) were evaluated by ELISA, and quantitative real-time PCR analyses were performed to evaluate the mRNA expression of NF-kB in peripheral blood mononuclear cells (PBMCs). Plasma malondialdehyde (MDA) levels, a peroxidation lipid marker, was measured as thiobarbituric acid reactive substances (TBARS). Routine parameters, including C-reactive protein (CRP), were analyzed using commercial kits. RESULTS All patients concluded the study: 10 patients in the propolis group [57.2 ± 13.7 years, five men, 6 (6–36) months on DP] and 9 in the placebo group [56.6 ± 14.7 years, two men, 6 (6–57) months on DP]. The obtained data revealed that the intervention did not affect the mRNA expression of NF-κB. However, the plasma levels of TNF-α reduced significantly after propolis supplementation (Table 1 and Fig. 1). There were no significant differences in the placebo group. CONCLUSION Short-term EPP-AF® propolis dry extract supplementation seems to mitigate inflammation, reducing the plasma levels of TNF-α in patients with CKD on PD.