Role Of Inflammatory Cytokines Research Articles

Osteoporosis in Rheumatic Diseases

The risk of osteoporosis and fragility fracture is increased in patients with autoimmune rheumatic diseases. Although the use of glucocorticoids is the major contributing factor, inflammation mediated by cytokines and growth factors and other medications, including the biologic and targeted disease-modifying antirheumatic drugs, also play important roles in bone remodeling. Pro-inflammatory cytokines such as IL-1, IL-6, IL-17, and TNF[Formula: see text] increase RANK expression and promote osteoclast activity while inhibiting osteoblast-mediated bone formation through the Dickkopf-1 pathway. Certain autoantibodies stimulate differentiation of the osteoclasts, resulting in localized bone resorption. This article covers the prevalence and risk factors for osteoporosis in patients with common rheumatic diseases and the role of inflammatory cytokines and other clinical factors. Controlling disease-related inflammation and optimizing the diagnostic and therapeutic instrumentation is needed to reduce fragility fractures in patients with rheumatic diseases.

State of the art of blue light effects on hidradenitis suppurativa: a concise systematic review

Introduction: In the setting of inflammatory diseases, hidradenitis suppurativa (HS), or acne inversa, is an immune-mediated skin disease with a prevalence of 0.1-1% and characterized by nodules and abscesses in the armpits, groin, and inframammary areas, which may evolve for fistulas and scars. Still, an update is needed on the recent understanding of the pathogenesis of HS, including the central role of inflammatory cytokines and other contributing factors such as genetics, hormones, and pathogenic microorganisms. As an innovative approach, antimicrobial blue light in the 400-470 nm spectrum has demonstrated its intrinsic antimicrobial properties resulting from the presence of endogenous photosensitizing chromophores in pathogenic microorganisms. Objective: To carry out a narrative and systematic review of the literature to explore the main clinical and experimental results of the use of photobiomodulation with blue light for the treatment of hidradenitis suppurativa by antibacterial action. Methods: The present study followed a model of narrative and systematic review, according to PRISMA rules, to gather the main information about the efficiency and safety of blue light in the treatment of HS. The research was carried out from January 2018 to May 2019 and developed based on Google Scholar, Scopus, PubMed, Scielo, and Cochrane Library. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results: Microorganisms are less able to develop resistance to antimicrobial blue light than to traditional antibiotics, due to the multi-targeting characteristics of antimicrobial blue light. Furthermore, it is well accepted that antimicrobial blue light is much less harmful to host cells than UV irradiation. Clinical studies have presented scientific evidence of treatment for HS with light-based therapy, showing efficacy and safety through articles published in quality journals in scientific evidence. A meta-analysis published in 2019, based on the quality of the evidence, showed that the most recommended treatments for HS include adalimumab and laser (blue light) therapy. For intense pulsed light with blue light, two RCTs reported improvements in HS-LASI scores and the Dermatology Quality of Life Index. Conclusion: The use of blue light for dermal treatments, particularly for HS, is finding an increasing role in dermatology. However, more robust and consistent studies are still needed to better demonstrate the antibacterial effects of blue light on HS.

Assessment of TNF-α expression in unstable atherosclerotic plaques, serum IL-6 and TNF-α levels in patients with acute coronary syndrome and rheumatoid arthritis.

The role of inflammatory cytokines is well researched in acute coronary syndrome (ACS) and rheumatoid arthritis (RA), but not in the presence of both conditions. This study aimed to compare TNF-α expression, serum TNF-α, IL-6, and hs-CRP in ACS patients with RA (n = 46) with ACS patients without RA (n = 49) and healthy controls (n = 50). TNF-α expression was assessed from coronary artery samples, taken during coronary artery bypass surgery. Serum levels TNF-α, IL-6, and hs-CRP were measured 24 and 48h after cardiac surgery. Stronger TNF-α expression was observed in the ACS patients with RA versus the ACS patients without RA, p = 0.001. Serum TNF-α, IL-6, and hs-CRP at the 24thh were significantly elevated in both patient groups and distinguished them from the healthy controls with accuracy ranging from 80 to 99%. At the 48th h, serum TNF-α and IL-6 in the ACS group without RA decreased to those of the healthy controls but remained high in the group with RA. ACS cases with RA could be correctly identified from the levels of IL-6 (AUC = 0.885, 95% CI 0.791 to 0.938) and TNF-α (AUC = 0.852, 95%CI 0.720 to 0.922). Our results suggest that the presence of RA in ACS cases is likely to provoke stronger TNF-α expression on atherosclerotic plaques, aggravate the pro-inflammatory response, and sustain it even after the cardiac stress is lowered. In ACS cases with RA, long-term monitoring and control of TNF-α and IL-6 levels can be a useful preventive strategy.

Association of Inflammatory Cytokines With Non-Alcoholic Fatty Liver Disease.

BackgroundInflammatory cytokines have been considered to be significant factors contributing to the development and progression of non-alcoholic fatty liver disease (NAFLD). However, the role of inflammatory cytokines in NAFLD remains inconclusive.ObjectiveThis study aimed to evaluate the association between inflammatory cytokines and NAFLD.MethodsPubMed, Web of Science, the Cochrane Library, and EMBASE databases were searched until 31 December 2021 to identify eligible studies that reported the association of inflammatory cytokine with NAFLD and its subtypes. We pooled odds ratios (ORs) and hazard risk (HRs) with 95% confidence intervals (CIs) and conducted heterogeneity tests. Sensitivity analysis and analysis for publication bias were also carried out.ResultsThe search in the databases identified 51 relevant studies that investigated the association between 19 different inflammatory cytokines and NAFLD based on 36,074 patients and 47,052 controls. The results of the meta-analysis showed significant associations for C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) with NAFLD (ORs of 1.41, 1.08, 1.50, 1.15 and 2.17, respectively). In contrast, we observed non-significant associations for interferon-γ (IFN-γ), insulin-like growth factor (IGF-II), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-7 (IL-7), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-12 (IL-12), monocyte chemoattractant protein-1(MCP-1), and transforming growth factor-β (TGF-β) with NAFLD. Our results also showed that CRP, IL-1β, and TNF-α were significantly associated with non-alcoholic steatohepatitis (NASH) and hepatic fibrosis.ConclusionsOur results indicated that increased CRP, IL‐1β, IL-6, TNF‐α, and ICAM-1 concentrations were significantly associated with increased risks of NAFLD. These inflammatory mediators may serve as biomarkers for NAFLD subjects and expect to provide new insights into the aetiology of NAFLD as well as early diagnosis and intervention.

Role of Inflammatory Cytokines in Pathophysiology of Psoriasis

Role of Inflammatory Cytokines in Pathophysiology of Psoriasis

Role of Inflammatory Cytokines in the Conversion of Mild Cognitive Impairment to Dementia: A Prospective Study.

The effect that cytokines can exert on the progression from mild cognitive impairment (MCI) to ongoing dementia is a matter of debate and the results obtained so far are controversial. The aim of the study is to analyze the influence of markers of subclinical inflammation on the progression of MCI to dementia. A prospective study involving a cohort of patients ≥ 65 years of age diagnosed with MCI and followed for 3 years was conducted. 105 patients were enrolled, and serum concentrations of several subclinical inflammatory markers were determined. After 3.09 (2 - 3.79) years of follow-up, 47 (44.76%) patients progressed to dementia. Alpha 1-antichymotrypsin (ACT) was found to be significantly higher in patients who progressed to dementia (486.45 ± 169.18 vs. 400.91 ± 163.03; p = 0.012), and observed to significantly increase the risk of developing dementia in patients with mild cognitive impairment (1.004, 1.001-1.007; p = 0.007). IL-10 levels were significantly higher in those who remained stable (6.69 ± 18.1 vs. 32.54 ± 89.6; p = 0.04). Regarding the type of dementia to which our patients progressed, we found that patients who developed mixed dementia had higher IL-4 levels than those who converted to AD (31.54 ± 63.6 vs. 4.43 ± 12.9; p = 0.03). No significant differences were observed between the groups with regard to the ESR and LPa, CRP, IL-1 and TNF-α levels. ACT levels have a significant predictive value in the conversion of MCI to dementia. IL-10 levels could be a protective factor. It is necessary to conduct studies with serial determinations of these and other inflammatory markers in order to determine their effect on the progression of MCI to dementia.

Cytokines in Schizophrenia: Predisposing Factors and Inflammatory Responses

Schizophrenia is a multifactorial disease that may be triggered by environmental disorders, mental stress, or physical illness in a person who is genetically predisposed to it. Recent research has extremely evaluated the role of inflammatory cytokines in schizophrenia. The current study attempted to find any association between cytokines and schizophrenia. This narrative study was conducted through a literature review in Scopus, PubMed, and Web of Science databases using keywords related to schizophrenia and cytokines without any time limitation. This review focused on discussing the relationship between various symptoms of disease and cytokine levels. Environmental factors such as embryonical infections were found to be associated with alternations in mothers’ blood cytokines and further effects on schizophrenia probability in children. Heritable factors including disrupted-in-schizophrenia 1 (DISC1) and neuregulin 1 (NRG1) genes were shown to be linked with immunological responses, as well as Toll-like receptors or AKT1/p13k activation and following alternations in the cytokine profile. Based on the findings, the cytokines and inflammatory responses of the body were reported to be involved in many psychological disorders and schizophrenia. Various interleukins (ILs), as well as IL-6, IL-8, and IL-2R are known to be associated with the severity of schizophrenia symptoms. Although various data exist regarding different cytokines and their association with schizophrenia, no study has so far formulated research fields on specific types of cytokines that have the potential to be further studied for therapeutic hope.

Role of Inflammatory Cytokines, Growth Factors and Adipokines in Adipogenesis and Insulin Resistance.

Obesity, manifested by increased adiposity, represents a main cause of morbidity in the developed countries, causing increased risk of insulin resistance and type 2 diabetes mellitus. Recruitment of macrophages and activation of innate immunity represent the initial insult, which can be further exacerbated through secretion of chemokines and adipocytokines from activated macrophages and other cells within the adipose tissue. These events can impact adipogenesis, causing dysfunction of the adipose tissue and increased risk of insulin resistance. Various factors mediate adiposity and related insulin resistance including inflammatory and non-inflammatory factors such as pro and anti-inflammatory cytokines, adipokines and growth factors. In this review we will discuss the role of these factors in adipogenesis and development of insulin resistance and type 2 diabetes mellitus in the context of obesity. Understanding the molecular mechanisms that mediate adipogenesis and insulin resistance could help the development of novel therapeutic strategies for individuals at higher risk of insulin resistance and type 2 diabetes mellitus.

The Cerebrospinal Fluid Presentations of Neuro-Bechet Disease, a Way to Know ‎the Etiopathogenesis and Improve Armamentarium‎.

Neuro-Behcet's disease (NBD) is a rare but potentially fatal manifestation of Behcet's disease. Common presentations of neuro-Behcet's disease are parenchymal (brainstem and hemispheric manifestations, meningoencephalitis, spinal cord lesions) and non-parenchymal (arterial occlusions, aneurysms, Dural sinus thrombosis). Cerebrospinal fluid (CSF) findings in parenchymal NBD usually show an inflammatory pattern with elevated cell count (usually high levels of polymorphonuclear leukocytes), high protein, and normal glucose levels, whereas the CSF findings in non-parenchymal NBD could be normal except for high opening pressure. Further investigation of CSF in parenchymal NBD has demonstrated elevated Natural killer T cells, high inflammatory chemokines, and cytokines such as Tumor Necrosis Factor-alpha (TNF- α), Interferon-gamma (IFN-γ), Interleukin (IL)12, IL-6, IL-17, IL-26, IL-15, Vascular endothelial growth factor (VEGF), Matrix metallopeptidase 9 (MMP-9), chemokine [C-X-C motif] ligand 8 (CXC-8) which indicate the role of both innate and adaptive immunity in this disease. Particularly, T helper type 1 (TH-1) and TH-17 pathways are implicated in the pathogenesis of this condition. Successful use of certain biologic agents such as TNF and IL-6 inhibitors in NBD further emphasizes the role of inflammatory cytokines in the immunopathogenesis of the disease. Drugs blocking the TH 17 pathway such as ustekinumab, secukinumab could also be applicable in the process. This review summarizes the detailed CSF findings in NBD, current understanding of the immunopathogenesis of NBD, and treatment of NBD with specific biologic agents based on our understanding of the disease pathogenesis.

Is there a common pathophysiological mechanism between COVID-19 and depression?

COVID-19 is a disease caused by SARS-CoV-2 and was initially considered to cause serious damage to the respiratory system. Over time, it has been found to affect other organs due to its ability to bind to the ACE2 receptor (type 2 angiotensin-converting enzyme), which can be found in various tissues, including the central nervous system. In addition, a large formation of pro-inflammatory cytokines responsible for various lesions was observed during the evolution of this disease. Our objective was to demonstrate the molecular mechanisms involved in the infection that may demonstrate the relationship between COVID-19 and the development of depressive conditions. Based on the main medical databases (LiLacs, SciELO, Bireme, Scopus, EBSCO, and PubMed) and using the terms 'coronavirus infections' AND 'Inflammation' AND 'depression' AND 'cytokines', we conducted an integrative review of articles published in 2020. Considering this stage of Covid-19 and the inflammatory component of depression, this review showed a relationship between these two conditions based on common pathophysiological mechanisms indicating possible depressive disorders in surviving patients, especially in the most severe cases. The role of inflammatory cytokines and the presence of ACE-2 receptors on the cell surface appear to be the common pathophysiological mechanism between COVID-19 and depression.

Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines’ molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications.

Subclinical atherosclerosis in patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis is an inflammatory disorder of the central nervous system. Inflammation may create high susceptibility to subclinical atherosclerosis. The purpose of this study was to compare subclinical atherosclerosis and the role of inflammatory cytokines between the group of patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls matched for age and sex. The study group consisted of 112non-diabetic and non-hypertensive RRMS patients treated with disease modifying drugs (DMD) and the control group was composed of 51healthy subjects. The common carotid artery (CCA) intima media thickness (IMT) was investigated. Serum levels of risk factors for atherosclerosis and inflammatory cytokines were also determined. The mean CCA IMT (0.572 ± 0.131 mm vs. 0.571 ± 0.114 mm) did not differ (p > 0.05) between patients and controls. The RRMS patients' CCA IMT was significantly correlated with serum interleukin6 (IL-6) (p = 0.027), high-sensitivity C-reactive protein (hs-CRP) (p = 0.027), cystatinC (p < 0.0005), glucose (p = 0.031), cholesterol (p = 0.008), LDL (p = 0.021), erythrocyte sedimentation rate (p = 0.001) and triglyceride (p = 0.018) level. We fitted generalized linear models in order to assess the relationship between CCA IMT and IL‑6 with adjustment for sex and age. The obtained results showed that adjusted for age (p < 0.001) and sex (p = 0.048) IL‑6 serum levels statistically significantly (p = 0.009) predict CCA IMT only in the RRMS group. The findings of the present study suggest that when treated with DMD RRMS might not be an independent risk factor for early atherosclerosis presenting with arterial wall thickening; however, the results suggest a significant association of IL‑6 serum levels with CCA IMT only in the RRMS group.

The role of inflammatory cytokines in anemia and gastrointestinal mucosal injury induced by foot electric stimulation

Foot electrical stimulation (FES) has been considered as a classic stressor that can disturb homeostasis. Acute anemia was observed in the model induced by FES. The aim of this study was to explore the role of inflammatory cytokines underlying the acute anemia and gastrointestinal (GI) mucosal injury in the FES. Twenty-four male Kunming mice (20 ± 2 g) were randomly divided into control group and experimental group. The mice were placed in a footshock chamber that can generate 0.5 mA electrical impulse periodically for 0.5 h. After the process, red blood cell count, hemoglobin concentration and hematocrit, the levels of corticotropin releasing hormone (CRH) in serum and hypothalamus, and adrenocorticotropic hormone (ACTH) in serum and pituitary were detected separately. In addition, we investigated the expressions of inflammatory cytokines (IL-1, IL-6, TNF-α, iNOS, and IL-10) in the hypothalamus and duodenum by Polymerase Chain Reaction (PCR). Results showed that this FES model induced anemia, increased CRH and ACTH activity in the serum after the FES. Moreover, the expressions of IL-1β, IL-6, TNF-α, and iNOS were significantly increased following the process, while IL-10 was not activated. These findings suggest that anemia, the inflammatory cytokines in the hypothalamus and duodenum of the mice in the model induced by FES is closely related to GI mucosal injury/bleeding. Taken together, these results underscore the importance of anemia, GI mucosal injury/bleeding and stress, future studies would be needed to translate these findings into the benefit of affected patients.

The Role of Inflammatory Cytokines as Intermediates in the Pathway from Increased Adiposity to Disease.

ObjectiveThis study aimed to investigate the role of cytokines as intermediates in the pathway from increased adiposity to disease.MethodsBMI and circulating levels of up to 41 cytokines were measured in individuals from three Finnish cohort studies (n = 8,293). Mendelian randomization (MR) was used to assess the impact of BMI on circulating cytokines and the impact of BMI‐driven cytokines on risk of obesity‐related diseases.ResultsObservationally, BMI was associated with 19 cytokines. For every SD increase in BMI, causal effect estimates were strongest for hepatocyte growth factor, monocyte chemotactic protein‐1 (MCP‐1), and tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL) and were as ratios of geometric means 1.13 (95% CI: 1.08‐1.19), 1.08 (95% CI: 1.04‐1.14), and 1.13 (95% CI: 1.04‐1.21), respectively. TRAIL was associated with a small increase in the odds of coronary artery disease (odds ratio: 1.03; 95% CI: 1.00‐1.06). There was inconsistent evidence for a protective role of MCP‐1 against inflammatory bowel diseases.ConclusionsObservational and MR estimates of the effect of BMI on cytokine levels were generally concordant. There was little evidence for an effect of raised levels of BMI‐driven cytokines on disease. These findings illustrate the challenges of MR when applied in the context of molecular mediation.

In silico dynamics of COVID-19 phenotypes for optimizing clinical management

Understanding the underlying mechanisms of COVID-19 progression and the impact of various pharmaceutical interventions is crucial for the clinical management of the disease. We developed a comprehensive mathematical framework based on the known mechanisms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, incorporating the renin-angiotensin system and ACE2, which the virus exploits for cellular entry, key elements of the innate and adaptive immune responses, the role of inflammatory cytokines, and the coagulation cascade for thrombus formation. The model predicts the evolution of viral load, immune cells, cytokines, thrombosis, and oxygen saturation based on patient baseline condition and the presence of comorbidities. Model predictions were validated with clinical data from healthy people and COVID-19 patients, and the results were used to gain insight into identified risk factors of disease progression including older age; comorbidities such as obesity, diabetes, and hypertension; and dysregulated immune response. We then simulated treatment with various drug classes to identify optimal therapeutic protocols. We found that the outcome of any treatment depends on the sustained response rate of activated CD8+ T cells and sufficient control of the innate immune response. Furthermore, the best treatment-or combination of treatments-depends on the preinfection health status of the patient. Our mathematical framework provides important insight into SARS-CoV-2 pathogenesis and could be used as the basis for personalized, optimal management of COVID-19.

That Gut Feeling: The Role of Inflammatory Cytokines in Depression Among Patients with Inflammatory Bowel Disease

There is mounting evidence of an associative link between inflammatory bowel disease (IBD) and clinical depression. In the first major treatise on the eponymous disease, Burrill Crohn himself noted that: “The number of cases of ileitis that have been rescued from institutions for the treatment of mental diseases emphasises not the personality but the end results of the drain of the disease upon the psychic constitution of the sufferer.” In the 70 years since that prescient statement, a high incidence of neuropsychiatric symptoms (depression, anxiety, cognitive fatigue, and sleep disorders) in patients with IBD has been frequently observed. Since patients with depression have significantly increased rates of relapse, surgery, hospitalisation, and suicide, recognising and treating depression is of paramount importance. In this narrative review, the authors will trace some of the biochemical connections between intestinal inflammation and neuropsychiatric symptoms and focus on strategies to manage both. Additionally, the authors offer a cautionary reflection on the extant need for widespread screening for depression among patients with IBD.

Severe Acute Respiratory Syndrome Coronavirus 2 and the Use of Biologics in Patients With Psoriasis [Formula: see text

Coronavirus disease (COVID-19), a respiratory disease caused by a novel coronavirus designated severe acute respiratory syndrome coronavirus 2, has rapidly spread worldwide and has been recognized as a pandemic by the World Health Organization. Patients with altered immunologic function are at higher risk of acquiring COVID-19. In patients with psoriasis, inhibition of select pro-inflammatory cytokines through the use of biologic agents has been shown to be an effective treatment option. Pro-inflammatory cytokines have key immunomodulatory effects and are known to be involved in the hosts' immune response to a variety of viral infections. Though little is currently known about the role of inflammatory cytokines in COVID-19, early reports have shown patients with severe disease to have elevated serum levels of select inflammatory cytokines such as tumor necrosis factor alpha. This review will summarize key information that is currently known about COVID-19, the role of select cytokines in viral defense, and important considerations for patients with psoriasis using biologic agents during this pandemic. Currently, there is insufficient evidence to discontinue biologic therapy in patients with psoriasis who have not tested positive for COVID-19. The decision to pause biologic therapy should be considered on a case-by-case basis in patients in higher risk populations, and should take into account individual risk and benefit. Until more is known about the impact of biologic therapy on COVID-19 outcomes, we recommend patients with psoriasis who test positive for COVID-19 be instructed to discontinue or postpone biologic treatment until they have recovered from infection.

The Role of Inflammatory Cytokine and Inflammatory Regulator Protein Related to Severity of Joint Effusion in Osteoarthritis

BACKGROUND: Osteoarthritis (OA) is an inflammatory degenerative articular disease characterized by damage narrowing the joint gap, pain, and loss of joint function. Joint effusion is a clinical feature often found in OA patients and believed to be directly proportional to the levels of pro-inflammatory cytokine, tumor necrosis factor (TNF)-alpha, and interleukin 1B (IL-1B), and various other regulatory proteins such as transcription factor proteins, nuclear factor of activated T-cells 1 (NFATC1), and chromosome 1 open reading frame 38 (C1orf38).&#x0D; AIM: The aim of the study was to explore the role of pro-inflammatory cytokine expression (TNF-alpha and IL-1B) and transcription regulatory proteins (NFATC1 and C1orf38) with the severity of joint effusion in OA patients.&#x0D; METHODS: This study was an observational study with a case series study approach. A total of 80 study subjects with OA joint effusions were included in the study. The diagnosis of OA was based on clinical and radiologic assessment from American College of Rheumatology. Data of clinical severity were assessed with Kellgren-Lawrence criteria, stroke test score, and Tegner Lysholm Knee Scoring Scale. Random blood examination was performed to obtain erythrocyte sedimentation rate (ESR) and qualitative C-reactive protein to evaluate the level of inflammation in the body. TNF-alpha, IL-1B, NFATC1, and C1orf38 levels were assessed in joint fluid using the enzyme-linked immunosorbent assay method. The correlation was analyzed with the Pearson correlation test (p = 0.05).&#x0D; RESULTS: The severity of OA joint effusion was not correlated to ESR (p adjusted = 0.169; r = 0.078), TNF-alpha (p adjusted = 0.112; r = −0.087), IL-1B (p adjusted = 0.136, r = −0.078), C1orf38 (p adjusted = 0.121; r = −0.088), and NFATC1 (p adjusted = 0.102; r = −0.081).&#x0D; CONCLUSION: Pro-inflammatory cytokines of TNF-alpha and IL-1B, and the transcription factors of pro-inflammatory cytokines gene expression, NFATC1, and C1orf38, did not correlate with the severity of joint effusion in OA.

Renal Afferent Nerve Activation and Arterial Pressure Control: Role of Inflammatory Cytokines in Hypertension

Neural control of the kidney as well as aberrant renal nerve signaling remain a primary focus of research in cardiovascular and renal disease, including hypertension. Recent preclinical reports employing targeted afferent renal nerve ablation have confirmed the central role for afferent renal nerves in the development of hypertension, including studies in the DOCA‐salt rat. Moreover, direct measurement of afferent renal nerve activity (ARNA) in DOCA‐salt rats revealed elevated tonic ARNA; however, the mechanisms contributing to the increased ARNA, and in turn hypertension, remain unaddressed. Renal inflammation is postulated to be a primary contributor to the aberrant ARNA in this model, due to the elevated pro‐inflammatory cytokines (IL‐1β, IL‐6, TNFα, MCP‐1, GRO/KC) present in the DOCA‐salt kidneys. Therefore, we aimed to directly test the role of these cytokines in modulating ARNA and concomitant cardiovascular responses in normotensive and DOCA‐salt rats. We hypothesized intrarenal inflammatory cytokine administration would increase ARNA and arterial pressure (AP) in both treatment groups.To interrogate this hypothesis, unilateral nephrectomized male Sprague Dawley rats (300–350g; n=16) were administered 100mg DOCA (s.c.) or silicone vehicle (n=8/group), followed by 3vweeks of high salt diet administered through drinking water (0.9% NaCl). Each animal then underwent an acute surgical preparation under isoflurane anesthesia (2%) to record AP, heart rate (HR), and ARNA responses to randomized intrarenal injection (10μL; 0.1 μg/μL) of the following cytokines: IL‐1β, IL‐6, TNFα, MCP‐1, GRO/KC, and 0.9% saline (VEH). ARNA responses were normalized to maximal afferent activation (%Amax) achieved by TRPV1‐agonist (capsaicin; 50μM) injection at end of protocol. Responses between and within treatment groups were analyzed by a repeated‐measures two‐way ANOVA (α=.05). Data presented as mean ± SEM. * p&lt;.05 vs. Vehicle; # p&lt;.05 vs. Saline.Prior to stimulation, baseline ARNA (4.9 ± 1.3 vs. 13.8 ± 2.1 %Amax) and AP (106 ± 2 vs. *151 ± 5 mmHg) were elevated in DOCA rats vs. vehicle controls. Compared to VEH responses, no changes from baseline ARNA, AP or HR responses were detected following IL‐1β, TNFα, MCP‐1, or GRO/KC injection. Compared to saline vehicle, IL‐6 injection produced an increase in ARNA in both VEH (5.9 ± 1.8 vs. #24.1 ± 5.4 %Amax) and DOCA rats (14.7 ± 2.2 vs. #24.1 ± 5.4 %Amax). Interestingly, AP decreased following IL‐6 injection in parallel to ARNA stimulation in VEH (1 ± 1 vs. −6 ± 2mmHg) and DOCA (0 ± 1 vs. −11 ± 4mmHg) compared to saline. No differences in responses between DOCA and VEH were detected.To summarize, IL‐6 injection increased ARNA in both VEH and DOCA supported our hypothesis; however, the corresponding depressor responses did not. Together, we conclude IL‐6 is a direct activator of ARNA independent of DOCA. Several studies have previously reported a depressor response following ARNA activation under anesthesia, so the central processing of ARNA may be altered under anesthesia compared to the conscious state, which is a limitation of this study. Current dose‐response studies and conscious preparations are underway to elucidate this important cardio‐renal‐neural axis in blood pressure homeostasis.Support or Funding InformationNIH R00HL141650 (CTB); R01HL116476 (JWO)

The role of inflammatory cytokines in the development of idiopathic subglottic stenosis.

Idiopathic subglottic stenosis (iSGS) is a debilitating extrathoracic obstruction involving the lower laryngeal and upper tracheal airway. It arises without a known antecedent injury or associated disease process. iSGS is a fibrotic disease marked histologically by excessive accumulation of fibrous connective tissue components of the extracellular matrix (ECM, i.e., collagen and fibronectin) in inflamed tissue, which leads to airway obstruction and clinical dyspnea. Diverse diseases in divergent organ systems are associated with fibrosis, suggesting common pathogenic pathways. One of the most common is sustained host inflammation. Recent investigations focusing on the inflammatory response associated with iSGS have sought to characterize the immunophenotype and cytokine profile of the airway scar in iSGS. While the role of the immune response as inciting event in iSGS remains unresolved, the centrality of an active immune response to the observed subglottic tissue remodeling is becoming more defined.