Role Of Cytokines In Pathogenesis Research Articles

Role of cytokines in pathogenesis, diagnosis and efficiency evaluation of immunotherapy in various variants of sclerotic lichen in women

Our aim was to evaluate diagnostic and pathogenetic significance of plasma cytokines (IL-20, IL-23, IL-10, TNFα, IFNγ) in the patients with various clinical and histological variants of sclerotic lichen and to assess opportunity for their use as effectiveness criteria of immunotherapy for this disease using a drug based on eukaryotic deoxyribonucleic acid (Derinat). The prospective cohort study included assessment of the clinical manifestations (itching and dyspareunia) and measurement of blood cytokine contents (IL-20, IL-23, IL-10, TNFα, IFNγ) in women (n = 114) with various clinical variants of sclerotic lichen (atrophic, sclerotic and sclerotic-atrophic) before and after immunotherapy with a nucleic acid-based drug (Derinat). Derinat was chosen due to the fact of being an agonist of Toll-like receptors, and a number of immunoregulatory effects, including the ability to modulate cytokine production and to exert a positive influence upon regeneration processes. In addition, based on visual inspection, vulvoscopy and morphohistochemical examination results (evaluation criteria: skin thickness, number of collagen fibers, severity of fibrosis and sclerosis, etc.), the corresponding subgroups were classified within the II group, i.e., 2.1 (minimal sclerotic signs, n = 14), and 2.2 (pronounced sclerotic signs, n = 20). The control group consisted of conditionally healthy women, without history or presence of vulvar pathology (n = 30), with an age ranging from 20 to 50 years. Along with cytokine assessment by enzyme immunoassay, the study used the data of clinical examination (anamnesis collection, examination, palpation, vulvoscopy), as well as complex morphohistochemical evaluation of vulvar tissues. In atrophic variant, we have observed an increase in plasma IL-23 content, along with decreased TNFα; in lichen sclerosis, a maximal increase in IL-20, IL-23, and IFNγ was revealed; in sclerotic form of sclerotic lichen variant with severe sclerotic features, maximally enhanced IL-20, IL-23, TNFα, IFNγ, along with minimal levels of IL-10 was registered, as compared with other groups. Immunotherapy using Derinate resulted into significant reduction in the clinical manifestations in sclerotic lichen, i.e., itching of the vulva and dyspareunia, as well as normalization of cytokine indexes. Our studies have demonstrated an opportunity of using plasma concentrations of IL-20, IL-23, IL-10, TNFα, IFNγ as biomarkers of sclerotic lichen variants, and as laboratory criteria for efficiency of immunotherapy.

Role of cytokines in pathogenesis and progression of nonalcoholic steatohepatitis

Role of cytokines in pathogenesis and progression of nonalcoholic steatohepatitis

Role of cytokines in pathogenesis of H. pylori induced gastric mucosal inflammation.

Helicobacter pylori gastritis is characterized by colonize the stomach and induce strong,specific local and systemic humoral and cell-mediated immunity. The aim of this study was toevaluate the level of several cytokines and their role in the pathogenesis of H. pylori gastritisand whether H. pylori stimulate the release of these cytokines. The levels of TH1 (IFN-γ andTNF-α) and TH2 (IL-4, IL-6 and IL-10) cytokines, as well as, inflammatory cytokines (IL-1αand IL-8) were determined. Most of the investigated cytokines (IL-1α, IL-6, IL-8, IL-10, IFNγ,TNF-α and GM-CSF) showed a significantly increased level in the sera of H. pylori gastricpatients as compared to subjects (control) with no infection which showed normal seruminterleukin levels. While IL-10 showed significant decrease when compared to subjects.These results conclude the pro-inflammatory cytokines ave a central role in thepathogenesis of H. pylori-induced mucosal inflammation.

Retraction: A. Amedei et al. Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies. Int. J. Mol. Sci. 2012, 13, 13438-13460.

We have been made aware that the title paper [1] contains text taken verbatim from previously published articles by Shyi-Jou Chen et al. [2] and Ghislain Opdenakker and Jo Van Damme [3].[...].

Cytokine network in adults with falciparum Malaria and HIV-1: increased IL-8 and IP-10 levels are associated with disease severity.

BackgroundCo-infection with malaria and HIV increases the severity and mortality of both diseases, but the cytokine responses related to this co-infection are only partially characterised. The aim of this study was to explore cytokine responses in relation to severity and mortality in malaria patients with and without HIV co-infection.MethodsThis was a prospective cross-sectional study. Clinical data and blood samples were collected from adults in Mozambique. Plasma was analysed for 21 classical pro- and anti-inflammatory cytokines, including interleukins, interferons, and chemokines.ResultsWe included 212 in-patients with fever and/or suspected malaria and 56 healthy controls. Falciparum malaria was diagnosed in 131 patients, of whom 70 were co-infected with HIV-1. The malaria patients had marked increases in their cytokine responses compared with the healthy controls. Some of these changes, particularly interleukin 8 (IL-8) and interferon-γ-inducing protein 10 (IP-10) were strongly associated with falciparum malaria and disease severity. Both these chemokines were markedly increased in patients with falciparum malaria as compared with healthy controls, and raised levels of IL-8 and IP-10 were associated with increased disease severity, even after adjusting for relevant confounders. For IL-8, particularly high levels were found in malaria patients that were co-infected with HIV and in those who died during hospitalization.InterpretationsOur findings underscore the complex role of inflammation during infection with P. falciparum, and suggest a potential pathogenic role for IL-8 and IP-10. However, the correlations do not necessarily mean any causal relationship, and further both clinical and mechanistic research is necessary to elucidate the role of cytokines in pathogenesis and protection during falciparum malaria.

The role of cytokines in lymphoma with anemia

This study was purposed to investigate the role of cytokines in pathogenesis of lymphoma-associated anemia. The levels of IFN-γ, IL-1β, IL-6, TNF-α and EPO in serum from 45 lymphoma patients and 12 normal controls were detected by using ELISA, the EPOR level on bone marrow cells were detected by flow cytometry, the CFU-E of bone marrow cultured in vitro was counted under inverted microscope. The results showed that 25 (55.6%) out of 45 newly diagnosed lymphoma patients had anemia before diagnosis, 13 (28.9%) had anemia during therapy, 7 (15.5%)never had anemia. The IFN-γ and TNF-α levels in serum of patients with moderate and severe anemia were significantly higher than those in patients with mild anemia and without anemia as well as normal controls. The EPO, IL-6 and IFN-γ levels correlated negatively with Hb concentration in patients, the EPOR level in patients without anemia significantly higher than that in patients with anemia and normal controls. The bone marrow CFU-E amount in patients showed positive correlation with Hb and EPOR levels. It is concluded that the increased IFN-γ, TNF-α and IL-6 may contribute to the anemia in lymphoma, and yet the EPO and EPOR levels are elevated to balance negative regulatory effects on hematopoiesis and maintain normal hematopoiesis.

Plasma Levels of CXCL1 (GRO-α) and CXCL10 (IP-10) are Elevated in Type 2 Diabetic Patients: Evidence for the Involvement of Inflammation and Angiogenesis / Angiostasis in this Disease State

Recent evidence has demonstrated that environment and genetic factors play pivotal roles in diabetes and its related complications. The significant contributory role of cytokines in pathogenesis of type 2 diabetes is also well documented. This study was aimed to examine and compare both CXCL1 (GRO-alpha) and CXCL10 (IP-10) circulating levels in type 2 diabetic patients and healthy controls. Peripheral blood samples were collected from 100 type 2 diabetic patients and 150 healthy controls. Circulating CXCL1 and CXCL10 levels were measured by ELISA. Elevated serum levels of both CXCL1 and CXCL10 were found in type 2 diabetic patients in comparison to controls. Elevated levels of CXCL1 and CXCL10 could possibly be used as a marker of inflammation and angiogenesis/angiostasis in type 2 diabetes.

RETRACTED: Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies

Multiple sclerosis, the clinical features and pathological correlate for which were first described by Charcot, is a chronic neuroinflammatory disease with unknown etiology and variable clinical evolution. Although neuroinflammation is a descriptive denominator in multiple sclerosis based on histopathological observations, namely the penetration of leukocytes into the central nervous system, the clinical symptoms of relapses, remissions and progressive paralysis are the result of losses of myelin and neurons. In the absence of etiological factors as targets for prevention and therapy, the definition of molecular mechanisms that form the basis of inflammation, demyelination and toxicity for neurons have led to a number of treatments that slow down disease progression in specific patient cohorts, but that do not cure the disease. Current therapies are directed to block the immune processes, both innate and adaptive, that are associated with multiple sclerosis. In this review, we analyze the role of cytokines in the multiple sclerosis pathogenesis and current/future use of them in treatments of multiple sclerosis.

Cytokines regulate neuronal gene expression: Differential effects of Th1, Th2 and monocyte/macrophage cytokines

Inflammatory mediators, including cytokines, contribute to neuronal and axonal dysfunction and cell death. To examine the roles of cytokines in pathogenesis and regeneration in the central nervous system (CNS), we analyzed effects of cytokines on early gene regulation (6h) in neuronal cultures, employing gene arrays. Our hypothesis is that neuronal gene expression is differentially regulated in vitro by cytokine mixtures typical of Th1 and Th2 T cells and monocytes/macrophages (M/M). Th1 and M/M cytokines showed similar patterns for regulation of numerous pathways including cytokine-receptor interactions, MAP kinase, toll like receptors, apoptosis, PPAR signaling, cell adhesion molecules (CAMS), antigen processing, adipocytokine, and JAK-STAT signaling. M/M cytokines uniquely regulated genes in T cell, B cell and ECM receptor signaling pathways. Th2 cytokines had few effects on pathways regulated by Th1 and MM cytokines, but uniquely regulated genes related to neuroactive ligand-receptors and calcium. Th1 and MM cytokines markedly upregulated a wide array of cytokine-related genes. Notably, M/M cytokines uniquely upregulated G-CSF, GM-CSF, CXCL5 and lymphotactin (Xcl1). Th2 cytokines did not upregulate cytokine-related genes, with the exception of CCL11 and FMS-like tyrosine kinase 1, a VEGF receptor. In neuroactive ligand-receptor pathways, Th1 and M/M cytokines upregulated gene expression for tryptophan hydroxylase. Th1 cytokines upregulated gene expression for GABA A receptor, delta, while Th2 cytokines downregulated GABA A receptor, gamma 3. Significant changes occurred in several genes in the wnt and Notch signaling pathways, which are highly conserved and play critical roles in neuronal and glial differentiation. In the ubiquitin–proteasome pathway, proinflammatory cytokine mixtures induced upregulation of several genes, notably ubiquitin D (Ubd/FAT10), ubiquitin ligase and several proteasomal proteins. In agreement with microarray results, QRT-PCR showed marked upregulation of gene expression for Ubd with Th1 and M/M, for transglutaminase 2 with M/M, and for arginase 1 with Th2 cytokines. Expression of Ubd in the nervous system has not been previously reported. Both message and protein for Ubd are expressed in neurons, and upregulated by pro-inflammatory cytokines. Transglutaminase 2 has been implicated in neurodegenerative diseases, and proposed as a therapeutic target. Upregulation of arginase by Th2 cytokines could be potentially neuroprotective by decreasing NO generation and enhancing neurite outgrowth. Our analysis of changes in neuronal gene expression at the time of initial exposure to an abnormal cytokine milieu provides the opportunity to identify early changes that could be reversed to prevent later irreversible neuronal damage and death in multiple sclerosis and other CNS diseases.

Comparison of the expression of cytokine genes in the bursal tissues of the chickens following challenge with infectious bursal disease viruses of varying virulence

BackgroundCytokines are important mediators and regulators of host responses against foreign antigen, with their main function to orchestrate the functional activities of the cells of the immune system. However little is known about the role of cytokines in pathogenesis and immune responses caused by infectious bursa disease virus (IBDV). The aim of this study was to examine the transcripts of cell-mediated immune response-related cytokine genes in the bursal tissues of chickens infected with IBDVs of varying virulence to gain an understanding of pathological changes and mechanisms of immunosuppression caused by IBDV infection and the immune responses evoked.ResultsReal-time quantitative PCR analysis revealed that the expression levels of both Th1 [interferon (IFN)-γ, interleukins (IL)-2 and IL-12p40] and Th2 (IL-4, IL-5, IL-13 and IL-10) cytokines were significantly up-regulated following challenge with the H strain (vvIBDV) and up to 2- and 30-fold, respectively (P < 0.05). Following infection with the Ts strain (cell-adapted virus) these cytokine transcripts were up-regulated at 5 days post-infection (dpi), 2- and 13-fold respectively (P < 0.05), while the expression levels of IL-2 and IL-4 were not significantly different (P > 0.05). A higher degree of cytokine expression was induced by the H strain compared with the Ts strain.ConclusionThe results indicate that the expression of cell-mediated immune-related cytokine genes is strongly induced by IBDV, especially by the vvIBDV, H strain and reveal that these cytokines could play a crucial role in driving cellular immune responses during the acute phase of IBDV infection, and the cellular immune responses caused by IBDV of varying virulence are through different signaling pathways.

Production of proinflammatory and immunoregulatory cytokines by inflammatory cells from periapical lesions in culture

The role of cytokines in pathogenesis of periapical lesions is not well understood. The aim of this study was to study the correlation between proinflammatory and immunoregulatory cytokines in periapical lesions and their relationship with cellular composition and clinical presentation. Inflammatory cells were isolated from 67 human periapical lesions and cultivated for 24 h. The levels of proinflammatory cytokines: interleukin-1 beta (IL-1beta), IL-6, IL-8 and tumour necrosis factor alpha (TNF-alpha) and immunoregulatory cytokines: transforming growth factor-beta (TGF-beta) and IL-10 were determined in culture supernatants using a fluorescent bead immunoassay or ELISA. The phenotype of cells was analysed by immunocytochemistry. Inflammatory cells from symptomatic lesions which contained higher proportion of granulocytes, secreted higher levels of IL-1, IL-6 and IL-8 compared with asymptomatic lesions. Large-size lesions contained lower percentages of mononuclear phagocytes, higher percentages of CD8(+) T cells and produced higher levels of TNF-alpha, IL-6 and IL-10 compared with small-size lesions. There were negative correlations between the concentrations of TGF-beta and proinflammatory cytokines. TGF-beta, added to cultures, downregulated the levels of proinflammatory cytokines more strongly than IL-10, independently of clinical presentation of the lesions. By contrast, exogenous IL-10 was mainly immunosuppressive in cultures of asymptomatic lesions. Symptomatic lesions are characterized by higher production of proinflammatory cytokines. Immunoregulatory cytokines are more important for suppression of inflammation in asymptomatic lesions and in this context the effect of TGF-beta is more potent and different from IL-10.

Effect of nitric oxide (NO) inhibitors 1400W, aminoguanidine and L-NAME in oral mucositis induced by 5-fluorouracil (5FU) in animals

8140 Background: Oral mucositis induced by antineoplastic drugs is an important, dose-limiting and costly side effect of cancer therapy. It has been well established the role of cytokines in pathogenesis of oral mucositis, and it was reported that these pro-inflammatory mediators are important inducers of NO synthesis, suggesting a possible role for NO on the inflammatory response of mucosítis. The aim of this study was to investigate the role of the non-selective NO inhibitor Nφ-Nitro-L-Arginine Methyl Ester (L-NAME) and the inducible NO synthase (iNOS) selective inhibitors 1400W, and aminoguanidine on oral mucositis induced by 5-FU. Methods: Oral mucositis was induced by two intraperitoneal (i.p) injections of 5-FU in the first and second days of the experiment (60 and 40 mg/Kg respectively) in male Golden Sirian hamsters, followed by check pouches mechanical trauma in the 4th day. L-NAME (5, 10 or 20mg/Kg, s.c.), aminoguanidine (5 or 10 mg/Kg, s.c.), 1400W (1 mg/Kg, s.c.) or saline (positive control) were administered one hour before the injections of 5-FU and daily until sacrifice, on the 10th day. Macroscopic and histopathological analyses were evaluated and graded. The MPO activity was also determined. Results: AG (10 mg/Kg) and 1400W reduced both macroscopic (p<0.05; n=8: AG=score 2 (1–3); 1400W=1(1–3) vs Saline=3(2–3)) and histological parameters (p<0.05; n=8: AG=score 1.5(1–3); 1400W=1(1–3) vs Saline=3(1–3)) of oral mucositis, associated with a reduction in MPO activity and increase of the animal survival when compared to the group of animals subjected to oral mucositis that received saline. In contrast, the administration of L-NAME (5, 10 or 20 mg/Kg) did not significantly reverse the inflammatory alterations induced by experimental mucositis. Conclusion: The results presented in this study suggest a role of NO on the pathogenesis of oral mucositis induced by 5-FU, via iNOS. However, the mechanisms of actions of NO in inflammatory events of mucositis still deserves further investigation. Financial support: CNPq No significant financial relationships to disclose.

Interleukin-1β responses to Mycoplasma pneumoniae infection are cell-type specific

Interleukin-1β (IL-1β) is a major proinflammatory cytokine that is involved in many important cellular functions such as proliferation, differentiation, and activation of different cell types. Its mature form is released from the cells in response to various bacterial and viral infections, and it plays a significant role in host defense. Mycoplasma pneumoniae is a small bacterium without a cell wall that causes tracheobronchitis and atypical pneumonia in humans following attachment to respiratory epithelium, as well as extrapulmonary infections. Very little is known about the role of cytokines in pathogenesis or the response of target cells to M.pneumoniae attachment. The purpose of this study was to investigate the ability of M. pneumoniae to induce IL-1β in human lung epithelial carcinoma A549 and in human monocytic U937 cell lines. Following M. pneumoniae infection, both IL-1β mRNA and protein were induced in A549 cells vs. no induction in uninfected cells; however, the protein remained inside the A549 cells. Similarly, M. pneumoniae infection strongly increased mRNA and extracellular protein levels in U937 cells, which unlike A549 cells did exhibit baseline constitutive levels. De novo IL-1β protein expression was verified by cycloheximide studies. M. pneumoniae infection did not affect constitutive caspase-1 mRNA or protein levels in either cell line. Reduced caspase-1 activity in A549 cell lysates suggests the presence of an endogenous caspase-1 inhibitory component in the A549 cells. These collective data confirm previous studies that show that M. pneumoniae is a potent inducer of cytokines following adherence to host target cells, and establish that IL-1β release in response to M. pneumoniae infection is cell-type specific, thus emphasizing the importance of carefully considering multiple cell types in M. pneumoniae pathogenesis studies involving both immune cells and cytokine release patterns.

Содержание фактора некроза опухоли А и интерлейкина-1 в сыворотке крови пациентов при аутоиммунных заболеваниях щитовидной железы

Thyroid hormones, antibodies to thyroglobulin, and cytokines tumor necrosis factor a (TNF-a) and interleukin 1 (IL-1) were measured in 14 patients with diffuse toxic goiter (DTG) and 6 patients with Hashimoto ’s autoimmune thyroiditis (AIT). Patients with DTG were examined in the presence of hyperthy- rosis and those with AIT in the presence of euthyrosis. The data indicate a relationship between the levels of TNF-a and thyroid hormones: negative correlation in hyperthyrosis and positive in euthyrosis. In addition, patients with AIT develop a direct correlation between TNF-a and serum titer of antithyroglobulin antibodies. Serum level of IL-1 do not increase. The results of this study confirm the hypothesis about important role of cytokines in pathogenesis of autoimmune diseases of the thyroid, namely, DTG and AIT.

Elevated serum CD30 in ileal pouch patients with a predisposition to pouchitis: Evidence for the role of Th2 cytokines in pathogenesis

Elevated serum CD30 in ileal pouch patients with a predisposition to pouchitis: Evidence for the role of Th2 cytokines in pathogenesis

Cytokines in rheumatic diseases.

IL-1 and related cytokines have multiple biologic activities relevant to the rheumatic diseases. In addition to mediating inflammatory and immune responses, these proteins regulate many aspects of connective tissue metabolism. The cytokines interact in complex cascades: because of this, and various technical reasons, the exact role of cytokines in the pathogenesis of rheumatic diseases remains uncertain. However, considerable experimental data suggest that the abnormal regulation of cytokines contributes to such siseases as inflammatory arthritis, systemic lupus erythematosus, scleroderma, and dermatomyositis. Animal models of these diseases have contributed to understanding the role of cytokines in pathogenesis. Furthermore, drugs useful in treating these diseases affect cytokine pathways; some cytokines, their antagonists, or related substances have been used therapeutically to treat rheumatic diseases. The therapeutic use of these agents will likely increase as knowledge about the role of cytokines in the pathogenesis of rheumatic diseases expands.