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Cytokine Network (cytokine + network)

Distribution by Scientific Domains

Medical Sciences	85%
Life Sciences	14%

Distribution within Medical Sciences

Immunology	49%
Neurology	16%

Selected Abstracts

Dysregulation of the Cytokine Network in the Uterus of the Diabetic Rat

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2001
SERGE PAMPFER
Insulin-dependent (type 1) diabetes is an auto-immune disorder that produces secondary complications in numerous non-immunological systems. Changes in the synthesis and action pattern of several cytokines have been associated with the development of these alterations. Based on the clinical facts that the pregnant and non-pregnant functions of the reproductive system are also disrupted by diabetes, our laboratory has decided to concentrate its research activities on the hypothesis that cytokines may be implicated in the uteropathy and embryopathy associated with the metabolic disorder. This review article summarizes our major findings concerning the synthesis of TNF-, and IL-1, in the uterus of diabetic rats, and in cultures of rodent uterine cells upon their exposure to high concentrations of glucose. The paper also reviews evidence that both the peri-implanting embryo and the epithelial cell layer lining the uterine lumen are targets for the deleterious influence of excess TNF-,. If confirmed in the uterus of diabetic patients, these observations may explain how cytokines contribute to the dysregulation of crucial reproductive events like menstruation and embryo implantation in humans. [source]

Increased Plasma Levels of Pro- and Anti-inflammatory Cytokines in Patients with Febrile Seizures

EPILEPSIA, Issue 8 2002
Miia Virta
Summary: ,Purpose: Pro- and antiinflammatory cytokines regulate the febrile response during infection. Febrile seizures (FSs) conversely are associated with rapid onset of high fever. Activation of the cytokine network has been shown in previous studies of FSs and cytokines. In this study, the association between cytokines and FSs was further investigated. Methods: Interleukin-1, (IL-1,), interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), interleukin-10, and tumor necrosis factor-, plasma levels were measured with enzyme-linked immunosorbent assay in 55 children with FSs and in 20 age-matched febrile controls immediately on arrival at the hospital. Cerebrospinal fluid cytokine levels also were measured in 16 FS children. Results: The plasma IL-1RA/IL-1, ratio (mean, 2,133 vs. 119; median, 790 vs. 105; p < 0.0001) and plasma IL-6 (mean, 41.7 pg/ml vs. 16.1 pg/ml; median, 19.6 pg/ml vs. 10.5 pg/ml; p = 0.005) were significantly higher in FS patients compared with control children. Logistic regression analysis was used to find the most significant predisposing factors for FSs. In this analysis, the high plasma IL-1RA/IL-1, ratio was the most significant factor connected to FSs (OR, 41.5; 95% CI, 4.9,352.8), but high plasma IL-6 also was significantly associated with FSs (OR, 5.3; 95% CI, 1.4,20.3). Conclusions: Present results support the hypothesis that the cytokine network is activated and could have a role in the pathogenesis of FS. [source]

T-cell interleukin-6 receptor binding in interferon-,-1b-treated multiple sclerosis patients

EUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2000
P. Bongioanni
Multiple sclerosis (MS) is a T-cell-mediated autoimmune demyelinating disease of the central nervous system, associated with an altered cytokine network. We previously assayed peripheral blood T-lymphocyte binding for two prototypic cytokines, tumour necrosis factor-, (TNF-,) and interleukin-6 (IL-6), and found that T cells from MS patients had significantly more TNF-, and IL-6 receptors than those from healthy controls. In the present work, paralleling a previous one on T-cell TNF-, binding, we studied the effect of interferon (IFN)-,-1b treatment on T-lymphocyte IL-6 binding in patients with relapsing,remitting MS. T cells from MS patients had significantly (P < 0.001) higher amounts of IL-6 receptors than those from controls [292 ± 6 vs. 228 ± 8 (mean ± SEM) receptors per cell, respectively], whereas the ligand-receptor affinity values were similar in the two groups [26.2 ± 0.7 and 25.7 ± 0.4 (mean ± SEM) pmoles/l, respectively]. After a 3-month IFN-,-1b treatment, they showed a significant decrease in IL-6 binding [266 ± 7 (mean ± SEM) receptors per cell]. After 6 and 9 months, T-cell IL-6 Bmax values were even lower [258 ± 8 and 251 ± 8 (mean ± SEM) receptors per cell]. Since an increased IL-6 binding might be linked to a lymphocyte activation, our data give further support for an enhanced immune response in patients with MS. Our data seem to demonstrate that the major effects of IFN-,-1b treatment result in a decrease of T-cell activation. [source]

Anandamide enhances IL-10 production in activated microglia by targeting CB2 receptors: Roles of ERK1/2, JNK, and NF-,B

GLIA, Issue 2 2010
Fernando Correa
Abstract The endocannabinoid system exhibits anti-inflammatory properties by regulating cytokine production. Anandamide (AEA) down-regulates proinflammatory cytokines in a viral model of multiple sclerosis (MS). However, little is known about the mechanisms by which AEA exerts these effects. Microglial cells are the main source of cytokines within the brain and the first barrier of defense against pathogens by acting as antigen presenting cells. IL-10 is a key physiological negative regulator of microglial activation. In this study we show that AEA enhances LPS/IFN,-induced IL-10 production in microglia by targeting CB2 receptors through the activation of ERK1/2 and JNK MAPKs. AEA also inhibits NF-,B activation by interfering with the phosphorylation of I,B,, which may result in an increase of IL-10 production. Moreover, endogenously produced IL-10 negatively regulates IL-12 and IL-23 cytokines, which in its turn modify the pattern of expression of transcription factorsinvolved in Th commitment of splenocytes. This suggeststhat by altering the cytokine network, AEA could indirectly modify the type of immune responses within the central nervous system (CNS). Accordingly, pharmacological modulation of AEA uptake and degradation might be a useful tool for treating neuroinflammatory diseases. © 2009 Wiley-Liss, Inc. [source]

Interferons as pathogenic effectors in autoimmunity

IMMUNOLOGICAL REVIEWS, Issue 1 2005
Roberto Baccala
Summary:, Interferons (IFNs) type-1 (IFN ,/,) and type-II (IFN-,) are the most pleiotropic molecules in the intricate cytokine network. This dominance arises from three crucial factors: (i) initiation of IFN-,/, and IFN-, production at the inception of most innate immune responses, which primes for the ensuing adaptive immune responses, primarily through the sine qua non upregulation of major histocompatibility complex and costimulatory molecules; (ii) magnification of their production and signaling by cross-talk between themselves, and synergistic or antagonistic effects on other cytokines; and (iii) direct or indirect initiation of transcription of hundreds of immunologically relevant genes. Considering that aberrant immune responses against self-molecules seem to depend on the same constituents and pathways as those against exogenous antigens, it follows that IFNs are also major effectors in the pathogenesis of autoimmunity. Here, we review the diverse biological effects of IFNs on the immune system, discuss findings pertaining to the nature of exogenous and endogenous stimuli that might induce IFN production through the engagement of Toll-like receptors, and summarize the detrimental and, in some instances, beneficial effects of IFNs in systemic and organ-specific autoimmune diseases. [source]

What is a role of haeme oxygenase-1 in psoriasis?

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2007
Current concepts of pathogenesis
Summary The skin is constantly exposed to endogenous and environmental pro-oxidant agents, which lead to harmful generation of reactive oxygen species (ROS). Healthy skin, being a potential target for oxidative stress, is equipped with a large number of defence mechanisms including antioxidant systems. This protection can be corrupted by an imbalance between ROS and antioxidants with pathological level of oxidants prevailing. There is a great body of evidence indicating that some inflammatory skin diseases, such as psoriasis, are mediated by oxidative stress. Keratinocytes of normal skin, the primary target for pro-oxidant agents, show strong expression of ROS-detoxifying enzymes. In addition, normal keratinocytes express haeme oxygenase (HO), an enzyme which might be involved in the protection of cells against oxidative stress. HO (inducible HO-1, constitutive HO-2 and HO-3) is the rate-limiting enzyme in haeme catabolism, which leads to the generation of biliverdin, iron, and carbon monoxide. HO-1 is a stress-responsive protein whose expression is induced by various oxidative agents. HO-1 is known for its cytoprotective, antioxidant and anti-inflammatory properties. Interestingly, a strong overexpression of HO-1 was observed in psoriatic skin. However, the role of HO-1 in psoriasis remains unclear. In this review, we will discuss some current concepts concerning pathogenesis of psoriasis and the contribution of HO-1 in skin inflammation to show the relationships between HO-1, ROS and cytokine network in psoriatic skin. We will try to answer a question whether enhanced HO-1 expression in keratinocytes results in beneficial or detrimental effect on the development and severity of psoriatic lesions. [source]

Growth factor attenuation of IFN,-mediated hepatocyte apoptosis requires p21waf,1

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2006
Christian T. McCullough
Summary Interferon gamma (IFN,) is an important mediator of inflammatory liver damage as part of a complex cytokine network. In vitro, IFN, induces hepatocyte apoptosis. We hypothesized that the hepatocyte response to IFN signalling is context-dependent, and that specific growth factors, via phosphatidylinositol 3 kinase (PI(3)K) and protein kinase B/Akt signalling pathways, confer a cytoprotective effect. We established an in vitro model of IFN,-mediated primary hepatocyte injury. We show that epidermal growth factor (EGF) and hepatocyte growth factor (HGF) attenuate the IFN,-induced hepatocyte apoptosis. IRF-1, but not p53, is required for IFN,-mediated apoptosis. The loss of p21waf,1 not only sensitizes the hepatocyte to IFN,-mediated injury but is required for survival factor mediated cytoprotection. We show that the PI(3)K inhibitor, LY294002, partially inhibits the apoptotic response of the hepatocyte to IFN,. In summary, we present evidence that a component of pro-apoptotic IFN, signalling in the primary hepatocyte occurs via the PI(3)K pathway. We show that the hepatocyte response to IFN, is modulated by external survival factors and that this survival signalling requires p21waf,1. [source]

Immunopathogenesis of psoriasis: focus on natural killer T cells

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2009
S Peternel
Abstract Psoriasis is a common inflammatory skin disease triggered by dysregulated immune response and characterized by hyperproliferation and altered differentiation of keratinocytes. Formation of psoriatic lesions is thought to be elicited by the complex cellular and cytokine network arising from the pathogenic interactions between keratinocytes and components of innate and acquired immune system. Natural killer T (NKT) cells are a heterogenous T-cell lineage that has been implicated in the pathogenesis of various autoimmune diseases including psoriasis. Due to the numerous functions of NKT cells that link innate and adaptive immunity, their role in psoriasis is complex and still elusive. We summarize the currently available literature data on this issue and discuss the possible role of NKT cells in the immunopathogenesis of this autoimmune disease. [source]

Leukemia Inhibitory Factor: An Important Regulator of Endometrial Function

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2004
Zdzis, awa Kondera-Anasz
Problem:, Leukemia inhibitory factor (LIF) is multifunctional cytokine that displays biological activities in different cells, including endometrial cells. The aim of this study is to describe implications of LIF on a physiological function of endometrium. Method of study:, The role of LIF in the endometrial function is reviewed and summarized from the available literature. Results:, LIF plays an important role in a physiological function of endometrium. In human endometrial LIF expression depends on cellular localizations, steroid hormones, menstrual stages and a local cytokine network. Stronger LIF expression exists in an endometrial epithelium during a luteal phase of the menstrual cycle, which coincides with the time of an implantation. The impairments of the endometrial LIF expression may play a significant role in the pathological processes involving implantation and the infertility. Conclusions:, There is a substantial evidence that LIF is a potential regulator of the endometrial function and might be one of the factors that play a key role in human reproduction. [source]

Cytokines, implantation and early abortion: re-examining the Th1/Th2 paradigm leads to question the single pathway, single therapy concept

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2003
Gérard Chaouat
Problem: Human in vitro fertilization (IVF) embryo transfer is accompanied by a low implantation rate even after a very successful IVF, and there are a certain number of ,idiopathic sterilities' which are due to repeated implantation failures. In the very same vein, the question of improving implantation rates is of prime importance in agricultural research to improve the management of livestock. Pre-implantation prenatal diagnosis cannot be accomplished in individuals who have a high rate of implantation failure, whether women undergoing IVF, or animals, during genetic cloning. Implantation cytokine networks need to be known in such a perspective. Methods: We review the evolution and theories in reproductive immunology, briefly deal with the complexity of implantation as a step by step developmental event, and then present some of our recent data in mice and human. Conclusions: We conclude that the T helper cell type 1/2 (Th1/Th2) paradigm, as useful as it has been to explain pregnancy, is no longer sufficient in view of the emerging complexity of the cytokine network at the materno-fetal interface. This is peculiarly true for implantation, which, as a step by step developmentally regulated process, involving inflammatory molecules, cannot fit into such a scheme. [source]

Cytokine and anti-cytokine therapy in asthma: ready for the clinic?

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2009
D. Desai
Summary Asthma is a common disease with an increasing prevalence worldwide. Up to 10% of these patients have asthma that is refractory to current therapy. This group have a disproportionate use of health care resources attributed to asthma, have significant morbidity and mortality and therefore represent an unmet clinical need. Asthma is a complex heterogeneous condition that is characterized by typical symptoms and disordered airway physiology set against a background of airway inflammation and remodelling. The inflammatory process underlying asthma is co-ordinated by a cytokine network. Modulating this network with biological therapy presents a new paradigm for asthma treatment. Clinical trials undertaken to date have underscored the complexity of the inflammatory profile and its relationship to the clinical features of the disease and have raised the importance of safety considerations related to these novel therapies. T helper type 2 cytokine blockade remains the most promising strategy, with anti-interleukin-5 reducing asthma exacerbations. Although anti-cytokine therapy is not yet ready for the clinic, the long-awaited possibility of new treatments for severe asthma is moving ever closer. [source]

Platelet-activating factor and human meningiomas

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2006
Y. Denizot
Meningiomas are common primary intracranial tumours. Platelet-activating factor (PAF) is an inflammatory and angiogenic lipid mediator involved in several types of cancer. The presence of PAF receptor (PAF-R) transcripts, the levels of PAF, the phospholipase A2 activity (PLA2, the enzymatic activity implicated in PAF formation) and the PAF acetylhydrolase activity (AHA, the PAF degrading enzyme) were investigated in 49 human meningiomas. PAF-R transcripts, PAF, PLA2 and AHA were detected in meningiomas. However, their levels did not correlate with biological parameters such as the tumour grade, the presence of associated oedema, necrosis, mitotic index as well as intensity of the neovascularization and chronic inflammatory response. In conclusion, PAF is present in meningiomas where it might act on tumour growth by altering the local angiogenic and/or cytokine networks as previously suggested for human breast and colorectal cancer. [source]

Cytokines, implantation and early abortion: re-examining the Th1/Th2 paradigm leads to question the single pathway, single therapy concept

Development of molecular immunoassay system for probiotics via toll-like receptors based on food immunology

ANIMAL SCIENCE JOURNAL, Issue 1 2008
Haruki KITAZAWA
ABSTRACT Recent interest has focused on the importance of intestinal immunity for the host defense, but to date, not much is known about the underlying mechanisms. The toll-like receptor (TLR) family plays an important role in host defense through recognizing bacterial pathogen-associated molecular patterns. Our recent research on the physiological function of food products has investigated the immunoregulatory effects of probiotic lactic acid bacteria (LAB) via TLR. Studies of swine, which often substitute for a human model, have demonstrated intestinal immunoregulation by the probiotic LAB mediated by TLR in the gut. On the basis of our study, efforts have also been made to develop a molecular immunoassay system for probiotic LAB and find novel immunostimulatory DNA sequences from probiotics and high potential immunobiotic LAB strains via TLR signaling. These findings may provide important clues at the molecular level on TLR signal transduction pathways and recognition mechanisms for the ligands. They also provide impetus to further delineate the activation mechanism of the innate immune response. In addition to identifying immunoregulatory factor immunogenics from LAB, a better understanding of intestinal immune regulation through cytokine networks holds out promise for basic food immunology research and the development of immunobiotic foods to prevent specific diseases. [source]