Role Of Inflammation In Pathogenesis Research Articles

Targeting the NLRP3 inflammasome in Rare hereditary blood disorder Fanconi Anemia

Abstract Fanconi anemia (FA) patients are at higher risk of developing bone marrow failure (BMF) or cancer upon exposure to potential threats like viral infections, bacterial infections, carcinogens, and mutagens. Deleterious mutations in FA genes cause multiple cellular defects which include impaired ability to repair DNA interstrand crosslink lesions in the nucleus and impaired removal of damaged mitochondria via mitophagy in the cytoplasm. Fancc-deficient mice exhibit enhanced inflammatory response and are hypersensitive to lipopolysaccharide-induced septic shock as a result of hematopoietic suppression. Considering the role of inflammation in pathogenesis of Fanconi anemia and bone marrow failure diseases in general, we asked whether inflammasome inhibition could be a promising therapeutic for the treatment of FA. Our studies demonstrate that MCC950, a small molecule inhibitor of the NLRP3 inflammasome, can protect Fancc null mice from LPS-induced hemopoietic suppression and septic shock as evidenced by increased survival rate of Fancc−/− mice. MCC950 partially rescues the thrombocytopenia in peripheral blood and partially restores the loss of megakaryocyte-erythroid progenitor (MEP) and granulocyte-macrophage progenitor (GMP) pools upon LPS challenge. Further, Treatment with MCC950 significantly improved the bone marrow colony-forming capacity of Fancc−/− bone marrow cells in vitro. Our studies demonstrate that MCC950, a small molecule inhibitor of the NLRP3 inflammasome, can protect Fancc null mice from LPS-induced hemopoietic suppression and septic shock and warrants further evaluation as a potential therapeutic strategy in FA.

Aortic Wall Inflammation in the Pathogenesis, Diagnosis and Treatment of Aortic Aneurysms

The role of inflammation in the development of aortic aneurysms is emerging, along with the potential diagnostic and therapeutical potential of this correlation. Abdominal aorta aneurysms have a strong inflammatory substrate since atherosclerosis, which is undoubtedly linked to inflammation, is also a predisposing factor to their formation. Yet, data have emerged that the development of thoracic aorta aneurysms involves several inflammatory pathways, although they were previously referred to as a non-inflammatory disease. Since aortic aneurysms are mainly asymptomatic during their clinical course until their complications-which may be lethal-serum biomarkers for their early diagnosis are a necessity. Studies highlight that inflammation molecules may have a critical role in that direction. In addition, imaging techniques that trace aortic wall inflammation are developed in order to predict aneurysm growth rates and sites vulnerable of rupture. Several anti-inflammatory agents have been also studied in animal models and clinical trials for the treatment of aortic aneurysms. This review highlights the role of inflammation in pathogenesis, diagnosis and treatment of aortic aneurysms.

Exploring the Inflammatory Pathogenesis of Colorectal Cancer.

Colorectal cancer is one of the most commonly diagnosed cancers worldwide. Traditionally, mechanisms of colorectal cancer formation have focused on genetic alterations including chromosomal damage and microsatellite instability. In recent years, there has been a growing body of evidence supporting the role of inflammation in colorectal cancer formation. Multiple cytokines, immune cells such T cells and macrophages, and other immune mediators have been identified in pathways leading to the initiation, growth, and metastasis of colorectal cancer. Outside the previously explored mechanisms and pathways leading to colorectal cancer, initiatives have been shifted to further study the role of inflammation in pathogenesis. Inflammatory pathways have also been linked to some traditional risk factors of colorectal cancer such as obesity, smoking and diabetes, as well as more novel associations such as the gut microbiome, the gut mycobiome and exosomes. In this review, we will explore the roles of obesity and diet, smoking, diabetes, the microbiome, the mycobiome and exosomes in colorectal cancer, with a specific focus on the underlying inflammatory and metabolic pathways involved. We will also investigate how the study of colon cancer from an inflammatory background not only creates a more holistic and inclusive understanding of this disease, but also creates unique opportunities for prevention, early diagnosis and therapy.

Association of neutrophil to lymphocyte ratio (NLR) with angiographic SYNTAX score in patients with non-ST-Segment elevation acute coronary syndrome (NSTE-ACS).

Introduction: Considering the role of inflammation in pathogenesis of atherosclerosis, we aimed to investigate the association of presentation neutrophil to lymphocyte ratio (NLR) with complexity of coronary artery lesions determined by SYNTAX score in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). Methods: From March 2018 to March 2019, we recruited 202 consecutive patients, who were hospitalized for NSTE-ACS and had undergone percutaneous coronary intervention in our hospital. The association of presentation NLR with SYNTAX score was determined in univariate and multivariate linear regression analysis. Results: Higher NLR was significantly associated with higher SYNTAX score (beta = 0.162, P = 0.021). In addition, older age, having hypertension, higher TIMI score, and lower ejection fraction on echocardiographic examination were significantly associated with higher SYNTAX score. TIMI score had the largest beta coefficient among the studied variables (TIMI score beta = 0.302, P < 0.001). In two separate multivariate linear regression models, we assessed the unique contribution of NLR in predicting SYNTAX score in patients with NSTE-ACS. In the first model, NLR was significantly contributed to predicting SYNTAX score after adjustment for age, sex, and hypertension as covariates available on patient presentation (beta = 0.142, P = 0.040). In the second model, NLR was not an independent predictor of SYNTAX score after adjustment for TIMI score (beta = 0.121, P = 0.076). Conclusion: In NSTE-ACS, presentation NLR is associated with SYNTAX score. However, NLR does not contribute significantly to the prediction of SYNTAX score after adjustment for TIMI score. TIMI risk score might be a better predictor of the SYNTAX score in comparison to NLR.

Inflammation and Stroke Risk: A New Target for Prevention.

New therapeutic approaches are required for secondary prevention of residual vascular risk after stroke. Diverse sources of evidence support a causal role for inflammation in the pathogenesis of stroke. Randomized controlled trials of anti-inflammatory agents have reported benefit for secondary prevention in patients with coronary disease. We review the data from observational studies supporting a role for inflammation in pathogenesis of stroke, overview randomized controlled trials of anti-inflammatory therapy in cardiac disease and discuss the potential implications for stroke prevention therapy.

The role of inflammation in pathogenesis of juvenile schizophrenia

IntroductionInflammation is now known to be a key factor in the development of schizophrenia. In this regard, the study of the pathogenic role of inflammation in the early stages of schizophrenic process is of particular importance, making it possible to assess its activity and to predict the development of the disease.ObjectivesTo compare the dynamics of inflammatory markers in blood of first-episode psychosis (FEP) patients and people at risk signs for schizophrenia in the course of the treatment. Juvenile depression (JD) with attenuated symptoms of schizophrenic spectrum (ASSS) was investigated as a risk group.MethodsThe patients aged 17-25 years (20 people, of which 10 FEP patients (F20) and 10 JD with ASSS ones (F32.1-2, F32.38, F32.8)) were examined at admission to the hospital and at discharge. The controls consisted of 10 healthy volunteers. Symptom severity was collected using PANSS, SOPS, SANS, HDRS. The inflammation markers (TNF-α, IL-6, IL-10, leukocyte elastase (LE), CRP, α1-proteinase inhibitor (α1-PI), anti-S100-beta antibodies) were determined in blood.ResultsAn increase of inflammatory markers in both groups compared to controls was found (p&lt;0,05). The highest values of IL-6, LE, CRP, α1-PI and anti-S100-beta antibodies in FEP patients were revealed (p=0,03). After the treatment, the positive trend of inflammatory markers in FEP patients (p&lt;0,05), but not in JD with ASSS patients was detected (except LE activity, p&lt;0,05).ConclusionsThe results confirm the pathogenic role of inflammation in the development of endogenous mental disorders. The inflammatory markers studied reflect the activity of the pathological process in the early stages of schizophrenia.DisclosureNo significant relationships.

Overcoming T-cell exhaustion in LCH: PD-1 blockade and targeted MAPK inhibition are synergistic in a mouse model of LCH

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by granulomatous lesions containing pathological CD207+ dendritic cells (DCs) with persistent MAPK pathway activation. Standard-of-care chemotherapies are inadequate for most patients with multisystem disease, and optimal strategies for relapsed and refractory disease are not defined. The mechanisms underlying development of inflammation in LCH lesions, the role of inflammation in pathogenesis, and the potential for immunotherapy are unknown. Analysis of the immune infiltrate in LCH lesions identified the most prominent immune cells as T lymphocytes. Both CD8+ and CD4+ T cells exhibited “exhausted” phenotypes with high expression of the immune checkpoint receptors. LCH DCs showed robust expression of ligands to checkpoint receptors. Intralesional CD8+ T cells showed blunted expression of Tc1/Tc2 cytokines and impaired effector function. In contrast, intralesional regulatory T cells demonstrated intact suppressive activity. Treatment of BRAFV600ECD11c LCH mice with anti-PD-1 or MAPK inhibitor reduced lesion size, but with distinct responses. Whereas MAPK inhibitor treatment resulted in reduction of the myeloid compartment, anti-PD-1 treatment was associated with reduction in the lymphoid compartment. Notably, combined treatment with MAPK inhibitor and anti-PD-1 significantly decreased both CD8+ T cells and myeloid LCH cells in a synergistic fashion. These results are consistent with a model that MAPK hyperactivation in myeloid LCH cells drives recruitment of functionally exhausted T cells within the LCH microenvironment, and they highlight combined MAPK and checkpoint inhibition as a potential therapeutic strategy.

The Role of Inflammation in Pathogenesis of Preeclampsia: An Investigation of interleukin-6, interleukin 10, and the Ratio

Introduction: Pre-eclampsia is a major cause of maternal mortality and morbidity, preterm birth, perinatal death, and intrauterine growth restriction in global maternity cases. Purpose: The study aims to investigate the role of pro-inflammatory and anti-inflammatory cytokines in the pathophysiology of preeclampsia. Method: In order to get cross sectional data, The study employed observation method. The serum IL-6 and IL-10 of the subjects with preeclampsia and normal pregnancies were measured. The systolic, diastolic blood pressures, and proteinuria of the subjects were also checked. The results were evaluated using the t-test, the Kruskal-Wallis test, and the Spearman correlation test (P

Intranasal interferon beta improves memory and modulates inflammatory responses in a mutant APP-overexpressing rat model of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by progressive cognitive decline. According to the critical role of inflammation in pathogenesis of AD and memory deficits, a cytokine with anti-inflammatory properties like interferon beta (IFNβ), currently used to slow down disease progression and protect against cognitive disturbance in multiple sclerosis, might be also an effective treatment in AD condition. This study aimed to answer if the intranasal (IN) administration of IFNβ with high CNS accessibility can alleviate memory impairments in a mutant APP-overexpressing rat model of AD through modulating inflammatory responses. To address this question, the lentiviruses carrying human amyloid protein precursor (APP) with the Swedish and Indiana mutations (LV-APPSw/Ind) were bilaterally injected in the hippocampus of adult rats. Memory performance was assessed using passive avoidance task on days 49 and 50 after injection. Moreover, the expression of glial markers (GFAP and Iba1) and pro-inflammatory (TNF-α, IL-1β and IL-6) and anti-inflammatory cytokines (IL-10) were evaluated in the hippocampus. Therapeutic effects of IN-administered IFNβ (0.5 μg/kg and 1 μg/kg doses, every other day from day 23 to 50 after lentivirus injection) were examined in the LV-APP-injected rats. Our results showed that over-expression of mutant human APP gene in the hippocampus led to learning and memory deficits concomitant with gliosis and pro-inflammatory responses. Interestingly, treatment of AD-modeled rats with IFNβ ameliorated memory impairments possibly through suppressing gliosis and shifting from pro-inflammatory toward anti-inflammatory status, suggesting that IFNβ may be a promising therapeutic agent to improve cognitive functions and modulate inflammatory responses in an AD-like neurodegenerative context.

RNA Sequencing Reveals Small and Variable Contributions of Infectious Agents to Transcriptomes of Postmortem Nervous Tissues From Amyotrophic Lateral Sclerosis, Alzheimer's Disease and Parkinson's Disease Subjects, and Increased Expression of Genes From Disease-Activated Microglia.

Nervous tissues from both humans with neurodegenerative diseases (NDD) and animals with genetic models of human NDD, such as rare monogenic causes of Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s disease (AD), and Parkinson’s disease (PD), show activated microglia, suggesting a potential causal role for inflammation in pathogenesis of NDD. We performed paired-end (PE) RNA sequencing (RNA seq) of total RNA’s extracted from frozen sections of cervical spinal cords from ALS and CTL subjects, frontal cortical gray matter ribbons of AD and CTL subjects, and ventral midbrains of PD and CTL subjects. Trimmed PE reads were aligned against the hg38 human transcriptome using Tophat2/Bowtie2 (ALS) or HISAT2 (AD and PD) and quantitated with Cufflinks. PE reads were also aligned using Bowtie2 against genomes from representative species of Toxoplasma gondii and Trichinella sp. T6 (parasitic infectious agents), Babesia microti and Borrelia burgdorferi (tick-vector borne agents), and Treponema denticola and Porphyromonas gingivalis, agents causing chronic gingivitis. Primary aligned reads of each agent in each tissue sample were quantitated with SAMtools. We found small percentages (<0.1%) of transcriptomes aligned with B. microti, B. burgdorferi, T. denticola, and P. gingivalis genomes and larger percentages aligned with T. gondii (0.1–0.2%) and Trichinella sp. T6 (1.0–1.1%) genomes. In AD specimens, but in no others, primary aligned transcriptome percentages, although small, approached significance for being greater in AD compared to CTL samples for B. burgdorferi (p = 0.067) and P. gingivalis (p = 0.068). Genes’ expressions in postmortem tissues of AD and ALS but not PD revealed significant changes among disease-associated microglial (DAM) genes. Infectious agents’ transcripts can be detected in RNA seq reads of both NDD and CTL tissues and vary from agent to agent. Expressions of Stage 1 and Stage 2 DAM genes significantly changed, suggesting the presence of Stages 1 and 2 DAM in our NDD tissue samples.

Preliminary Study on the Relationship Between Inflammation and Hemifacial Spasm

Complete pathogenesis of hemifacial spasm (HFS) is unknown. In some patients with HFS, thickened, opaque, and sticky arachnoid membranes have been found during microvascular decompression procedures. This phenomenon indicates a possible relationship between inflammation and HFS. The aim of this study was to explore the role of inflammation in pathogenesis of HFS. Levels of interferon-γ, interleukin-2 receptor, interleukin-6 (IL-6), interleukin-8, interleukin-10, and tumor necrosis factor α and white blood cell (WBC), neutrophil, and lymphocyte counts were compared between patients with HFS, patients with lumbar disc herniation, and healthy control subjects. A receiver operating characteristic curve analysis was performed to evaluate the diagnostic significance of peripheral blood inflammatory markers for HFS. All the inflammatory markers were further analyzed by single and multiple logistic regression analysis. Patients with HFS had greater IL-6, interleukin-8, white blood cell count, and neutrophil count than patients with lumbar disc herniation and healthy control subjects. Area under curve values of IL-6, white blood cell count, and neutrophil count were >0.8. Multiple logistic regression analysis indicated that only interleukin-2 receptor and IL-6 were relevant to HFS. Inflammation is relative to HFS. IL-6 may be 1 of many factors involved in pathogenesis of HFS.

Primary neuronal culture as a source for direct reprogramming of the cells

Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by progressive cognitive decline. According to the critical role of inflammation in pathogenesis of AD and memory deficits, a cytokine with anti-inflammatory properties like interferon beta (IFNβ), currently used to slow down disease progression and protect against cognitive disturbance in multiple sclerosis, might be also an effective treatment in AD condition. This study aimed to answer if the intranasal (IN) administration of IFNβ with high CNS accessibility can alleviate memory impairments in a mutant APP-overexpressing rat model of AD through modulating inflammatory responses. To address this question, the lentiviruses carrying human amyloid protein precursor (APP) with the Swedish and Indiana mutations (LV-APPSw/Ind) were bilaterally injected in the hippocampus of adult rats. Memory performance was assessed using passive avoidance task on days 49 and 50 after injection. Moreover, the expression of glial markers (GFAP and Iba1) and pro-inflammatory (TNF-α, IL-1β and IL-6) and anti-inflammatory cytokines (IL-10) were evaluated in the hippocampus. Therapeutic effects of IN-administered IFNβ (0.5 μg/kg and 1 μg/kg doses, every other day from day 23 to 50 after lentivirus injection) were examined in the LV-APP-injected rats. Our results showed that over-expression of mutant human APP gene in the hippocampus led to learning and memory deficits concomitant with gliosis and pro-inflammatory responses. Interestingly, treatment of AD-modeled rats with IFNβ ameliorated memory impairments possibly through suppressing gliosis and shifting from pro-inflammatory toward anti-inflammatory status, suggesting that IFNβ may be a promising therapeutic agent to improve cognitive functions and modulate inflammatory responses in an AD-like neurodegenerative context.

The role of inflammation in pathogenesis and treatment of colorectal cancer

One of the factors affecting the effectiveness of treatment and determining the prognosis of a patient with colorectal cancer may be inflammatory status both before and after surgical treatment. The review is devoted to the description of possible mechanisms of relationa between patient's inflammatory status and oncogenesis. Particular attention is paid to the ability of tumor cells to modify the immune cells from the antioncogenic to prooncogenic status. The paper makes an attempt to present a unified concept of the impact of postoperative complications on tumor recurrence in the light of the inflammatory response to surgical intervention.

Serum-soluble CXCL16 in juvenile systemic lupus erythematosus: a promising predictor of disease severity and lupus nephritis.

Juvenile systemic lupus erythematosus (jSLE) is a multisystem autoimmune disease of unpredicted course and prognosis. Rates of organ involvement in SLE are higher in children, and overt lupus nephropathy is more often a presenting manifestation of SLE in children than adults. Inflammatory soluble chemokine CXC motif-ligand 16 (sCXCL16) is an important pathogenic mediator in inflammatory diseases as SLE. Herein, we aimed to evaluate serum level of sCXCL16 in jSLE patients in comparison to healthy controls and to correlate it with disease activity and extent of cutaneous and renal affection, to detect its possible role in disease pathogenesis. Serum level of sCXCL16 was determined by ELISA in 27 patients with jSLE (mean age 12.35years ± 2.26 SD) in addition to 30 age- and sex-matched healthy controls and correlated with clinical and laboratory parameters in lupus group. Serum sCXCL16 was significantly higher in jSLE patients than controls (P≤ 0.001), and it correlated positively with SLE disease activity, severity of lupus nephritis, 24-h urinary protein, anti-dsDNA titre, blood pressure, and ESR, while it correlated negatively with serum C3 levels. Serum sCXCL16 was higher in jSLE patients with alopecia and malar erythema. Serum sCXCL16 might play a role in inflammatory pathogenesis of jSLE particularly in periods of disease activity. It might serve as a future useful laboratory test for detection of jSLE activity, renal insult, and its severity which might limit the need for invasive renal biopsies in such a delicate patient population.

Immunoporosis: Immunology of Osteoporosis-Role of T Cells.

The role of immune system in various bone pathologies, such as osteoporosis, osteoarthritis, and rheumatoid arthritis is now well established. This had led to the emergence of a modern field of systems biology called as osteoimmunology, an integrated research between fields of immunology and bone biology under one umbrella. Osteoporosis is one of the most common inflammatory bone loss condition with more than 200 million individuals affected worldwide. T helper (Th) cells along with various other immune cells are major players involved in bone homeostasis. In the present review, we specifically discuss the role of various defined T lymphocyte subsets (Th cells comprising Th1, Th2, Th9, Th17, Th22, regulatory T cells, follicular helper T cells, natural killer T cells, γδ T cells, and CD8+ T cells) in the pathophysiology of osteoporosis. The study of the specific role of immune system in osteoporosis has now been proposed by our group as “immunoporosis: the immunology of osteoporosis” with special emphasis on the role of various subsets of T lymphocytes. The establishment of this new field had been need of the hour due to the emergence of novel roles of various T cell lymphocytes in accelerated bone loss observed during osteoporosis. Activated T cells either directly or indirectly through the secretion of various cytokines and factors modulate bone health and thereby regulate bone remodeling. Several studies have summarized the role of inflammation in pathogenesis of osteoporosis but very few reports had delineated the precise role of various T cell subsets in the pathobiology of osteoporosis. The present review thus for the first time clearly highlights and summarizes the role of various T lymphocytes in the development and pathophysiology of osteoporosis, giving birth to a new field of biology termed as “immunoporosis”. This novel field will thus provide an overview of the nexus between the cellular components of both bone and immune systems, responsible for the observed bone loss in osteoporosis. A molecular insight into the upcoming and novel field of immunoporosis would thus leads to development of innovative approaches for the prevention and treatment of osteoporosis.

Efficacy of anti-IL-23 monotherapy versus combination therapy with anti-IL-17 in estrogen deficiency induced bone loss conditions.

Recent studies have identified that Interleukin (IL)-23/IL-17 axis plays crucial role in pathogenesis of inflammation and bone destruction. IL-23 is thought to promote joint destruction in arthritis by stimulating Th17 cells. IL-23 directly mediates bone loss by inducing osteoclastogenesis and receptor activator of kappa B ligand (RANKL) expression in T cells. IL-23 also promotes tartrate-resistant acid phosphatase (TRAP) activity of osteoclast in osteoblast-osteoclast co-culture. The role of IL-23 has not been studied in estrogen deficiency induced bone loss. Here, we study the effect of IL-23 neutralization in ovariectomized (Ovx) estrogen deficient mice on various immune and skeletal parameters. We also determine whether the combination of anti-IL-23 and anti-IL17 has enhanced osteoprotective effects compared to monotherapies. Treatment of anti-IL-23 and its combination with anti-IL-17 suppressed Th17 cell differentiation and promoted development of T regulatory cells. Anti-IL-23 and its combination with anti-IL-17 prevented bone loss. However, the individual monotherapies of anti-IL-23 and anti-IL-17 were more effective than combination therapy. Treatment of IL-17 and IL-23 cytokines to bone marrow stromal cells led to increased differentiation towards osteoblast lineage. Double neutralization of IL-23 and IL-17 might be inhibiting this phenomenon thus producing less potent effects. Our studies thus support bone protective effects of anti-IL-23 and that the monotherapies of neutralizing antibodies against IL-17 and IL-23 may be a more accepted mode of treatment in management of post-menopausal bone loss rather than combination therapy.

NIMESULIDE IN TREATMENT OF ACUTE AND CHRONIC PAIN IN CLINICAL PRACTICE

The most common reason for a patient to contact a doctor is the pain accompanying about 70% of all known diseases. The article introduces the basic principles for treating acute and chronic pain. The role of inflammation in pathogenesis of acute and chronic pain is shown. It provides information on the effectiveness and safety of a non-steroid anti-inflammatory drug (NSAIDs) Nimesulide in the treatment of acute and chronic pain. Information is provided on the variety of Nimesulide mechanisms that allow it to be used in various rheumatic diseases as well as in other areas of medicine. The results of clinical research and analyses are presented that confirm the high efficiency and good tolerability of Nimesulide. The years of experience in the application of the granular form of Nimesulide (Nimesil®) by domestic clinicians indicate a high rate of development and a expressed anagesic, anti-inflammatory effects combined with good tolerability, which makes it possible to use the drug successfully in treating acute and chronic pain.

Irisin modulates the association of interleukin-17A with the presence of non-proliferative diabetic retinopathy in patients with type 2 diabetes.

The role of inflammation in pathogenesis of diabetic retinopathy (DR) is getting increasingly recognized. However, it is unclear whether and how non-proliferative diabetic retinopathy (NPDR) is affected by Interleukin-17A (IL-17A) and Interleukin-22 (IL-22), two well-known inflammatory factors, and irisin, a novel potential anti-inflammatory factor. Here we recruited 40 type 2 diabetes mellitus (T2DM) patients with NPDR, 60 T2DM patients without DR (no-DR), and 20 normal glucose tolerance (NGT) controls. Serum levels of IL-17A, IL-22, and irisin were examined. Compared with NGT and no-DR subjects, NPDR group had significantly higher IL-17A levels. Irisin levels were significantly lower in T2DM patients, while IL-22 levels were not significantly different across all three groups. Multiple logistic regression analysis revealed that IL-17A significantly increased the risk of NPDR (OR=1.22, P<0.05) before adjusting for irisin. When irisin was included in the model, neither irisin nor IL-17A was associated with NPDR. Further partial correlation analysis showed that irisin was intrinsically correlated with IL-17A even after multiple adjustment (r=-0.252; P=0.018). These findings suggest that IL-17A is an independent risk factor of NPDR, and irisin could protect against DR through potential anti-IL-17A effects.

The role of inflammation and cell death in the pathogenesis, progression and treatment of heart failure.

Chronic inflammation underlies a variety of seemingly unrelated conditions including coronary artery disease. The interest in exploring the role of inflammation in heart failure (CHF) arises from earlier observations that circulating pro-inflammatory biomarker levels are elevated in patients with both ischaemic and non-ischaemic cardiomyopathies and correlate with severity of disease and prognosis (McMurray et al. in Eur Heart J 33:1787-1847, 2012; Mosterd and Hoes in Heart 93:1137-1146, 2007; Owan et al. in New Engl J Med 355:251-259, 2006). In acute decompensated HF, pro-inflammatory biomarker levels have been associated with mortality and readmission rates (Cowie et al. in Heart 83:505-510, 2000). Similar to neurohormonal activation and inflammation, production of pro-inflammatory cytokines is a response to stress in an attempt to restore cellular function. However, sustained expression and exposure to cytokines can lead to left ventricular dysfunction, negative inotropic effects, altered cardiac metabolism, myocardial remodelling and HF progression. However, it is unclear whether elevated levels of pro-inflammatory biomarkers, such as high-sensitivity C-reactive protein, signify an ongoing inflammatory process that leads to HF progression, or are merely markers of advanced disease. Beta-blockers, renin-angiotensin-aldosterone axis antagonists, statins and immunosuppressants have been found to decrease the levels of cytokines in small clinical studies of patients with HF (Hobbs et al. in Heart J 28:1128-1134, 2007). However, 'immunomodulatory' approaches applied in the RECOVER, RENAISSANCE, ATTACH, IMAC and ACCLAIM double-blind, placebo-controlled studies had neutral or negative effects on outcomes of patients with HF. In the present review, we focus on the role of inflammation in pathogenesis and progression of the HF, the value of pro-inflammatory cytokines as biomarkers and the potential therapeutic applications of immunomodulation in HF patients.

Influance of regular swimming on serum levels of CRP, IL-6, TNF-α in high-fat diet-induced type 2 diabetic rats.

Due to key role of inflammation in pathogenesis of type 2 diabetes mellitus (T2DM), aim of this study was evaluating the influance of regular swimming on serum levels of C-reactive protein (CRP), interlukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in high-fat diet-induced diabetic rats. Fourty male Wistar rats were randomly divided into control, diabetic, exercise and diabetic-exercise groups (n = 10). Diabetes was induced by high-fat diet and streptozotocin (35 mg/kg, i.p.). In exercise groups, after induction of diabetes, animals were subjected to swimming (60 min/5 days a week) for 10 weeks. At the end of training, rats were anestatized and blood samples and pancreatic tissues were collected and used for evaluation of CRP, IL-6, TNF-α and pancreatic histopatholology. Our results showed significantly increase in lymphocytes, monocytes and decrease in neutrophils in diabetic rats (p < 0.01), which these parameters significantly reversed to control levels by induction of swimming (p < 0.01). In diabetic group, the levels of CRP, IL-6 and TNF-α increased (p < 0.01), and swimming decreased these factors significantly. Histopathological results of this study also showed that swimming can prevent damage induced by diabetes. The present study indicates that swim training is associated with improved inflammation and inflammatory mediators and pancreatic damage.