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Cytokine IL-10 (cytokine + il-10)

Distribution by Scientific Domains
Medical Sciences71%
Life Sciences28%
Distribution within Medical Sciences
Immunology32%
Allergy & Clinical Immunology12%

Kinds of Cytokine IL-10

  • anti-inflammatory cytokine il-10
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    Selected Abstracts

    Procoagulant and inflammatory response of virus-infected monocytes

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2002
    J. J. M. Bouwman
    Abstract Background Monocytes play a prominent role in inflammation, coagulation and atherosclerosis by their ability to produce tissue factor (TF) and cytokines. The aim of the present study was to establish whether virus-infected monocytes initiate coagulation. In addition, the production of cytokines by monocytes may accelerate the chronic process of atherosclerosis and may contribute to coronary syndromes by eliciting plaque instability. Materials and methods Monocytes were isolated by Vacutainer®, BD Biosciences, Alphen aan den Rijn, Netherlands and subsequent magnetic cell sorting (MACS®, Milteny Biotec, Bergish Gladbach, Germany). Coagulation times in normal pooled plasma and Factor VII-deficient plasma were measured after infection with cytomegalovirus (CMV), Chlamydia pneumoniae (Cp) and influenza A\H1N1. Anti-TF antibodies were added to neutralize TF expressed on monocytes. Interleukins (IL) 6, 8 and 10 were measured in the supernatants. Results Chlamydia pneumoniae- and CMV-infected monocytes decreased the clotting time by 60%, and influenza-infected monocytes by 19%, as compared to uninfected monocytes. Procoagulant activity was absent when Factor VII-deficient plasma or anti-TF antibodies were used. Monocytes produced both IL-6 and IL-8 after infection with CMV (317 pg mL,1 and 250 pg mL,1) or Cp (733 pg mL,1 and 268 pg mL,1). Similar results were obtained for influenza virus-infected monocytes, but the levels of both cytokines were 3,5-fold higher (1797 pg mL,1 and 725 pg mL,1). Interleukin-10 was not produced by infected monocytes. Conclusion The procoagulant activity of virus-infected monocytes is TF-dependent. Although influenza infection did not generate a significant reduction in clotting time, the pronounced expression of IL-6 and IL-8 may induce local and/or systemic inflammatory reactions, which may be associated with plaque rupture and atherosclerosis. The lack of production of the anti-inflammatory cytokine IL-10 may even accelerate these processes. [source]

    Nramp1 -functionality increases iNOS expression via repression of IL-10 formation

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2008
    Gernot Fritsche
    Abstract In mice, resistance to certain intracellular microbes depends on the expression of a late phagosomal protein termed natural-resistance associated macrophage protein 1 (Nramp1, Slc11a1). Nramp1- functionality is associated with alterations of cellular iron homeostasis and a sustained pro-inflammatory immune response, including the formation of the antimicrobial effector molecule NO. To investigate the underlying mechanism we used RAW-264.7 murine macrophage cells stably transfected with a functional Nramp1 allele (RAW-37) or Nramp1 non-functional controls (RAW-21). We found that the production of and signalling by the anti-inflammatory cytokine IL-10 was significantly enhanced in macrophages lacking functional Nramp1. Upon infection of macrophages with Salmonella typhimurium pathogen survival was significantly better in RAW-21 than in RAW-37, which inversely correlated to NO and TNF-, formation. Addition of a neutralising anti-IL-10 antibody to RAW-21 cells led to a significantly reduced survival of S. typhimurium within these cells and enhanced formation of NO and TNF-, reaching levels comparable to that observed in cells bearing functional Nramp1. Oppositely, supplementation of iron to RAW-21 cells further increased IL-10 formation. Thus, Nramp1 mediates effective host defence in part via suppression of excessive IL-10 production which may relate to Nramp1- mediated reduction of cellular iron pools, thus strengthening antimicrobial effector mechanisms. [source]

    A clinical pharmacological study of the potential beneficial effects of a propolis food product as an adjuvant in asthmatic patients

    FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2003
    M. T. Khayyal
    Abstract The aqueous extract of propolis has been formulated as a nutritional food product and administered, as an adjuvant to therapy, to patients with mild to moderate asthma daily for 2 months in the framework of a comparative clinical study in parallel with a placebo preparation. The diagnosis of asthma was made according to the criteria of patient classification of the National Institutes of Health and Global Initiative for Asthma Management. At inclusion, the pulmonary forced expiratory volume in the first second (FEV1) as a percentage of the forced vital capacity (FVC) was more than 80% in mild persistent cases, and between 60 and 80% in moderate persistent cases, showing an increase in the degree of reversibility of >,15% in FEV1. All patients were on oral theophylline as controller therapy, none was receiving oral or inhaled corticosteroids, none had other comorbidities necessitating medical treatment, and all were from a middle-class community and had suffered from asthma for the last 2,5 years. Twenty-four patients received the placebo, with one drop-out during the study, while 22 received the propolis extract, with no drop-outs. The age range of the patients was 19,52 years; 36 were male and 10 female. The number of nocturnal attacks was recorded on a weekly basis, while pulmonary function tests were performed on all patients at the beginning of the trial, 1 month later and at the termination of the trial. Immunological parameters, including various cytokines and eicosanoids known to play a role in asthma, were measured in all patients at the beginning of the trial and 2 months later. Analysis of the results at the end of the clinical study revealed that patients receiving propolis showed a marked reduction in the incidence and severity of nocturnal attacks and improvement of ventilatory functions. The number of nocturnal attacks dropped from an average of 2.5 attacks per week to only 1. The improvement in pulmonary functions was manifested as a nearly 19% increase in FVC, a 29.5% increase in FEV1, a 30% increase in peak expiratory flow rate (PEFR), and a 41% increase in the forced expiratory flow rate between 25 and 75% of the vital capacity (FEF25-75). The clinical improvement was associated with decreases by 52, 65, 44 and 30%, respectively, of initial values for the pro-inflammatory cytokines tumor necrosis factor (TNF)-,, ICAM-1, interleukin (IL)-6 and IL-8, and a 3-fold increase in the ,protective' cytokine IL-10. The levels of prostaglandins E2 and F2, and leukotriene D4 were decreased significantly to 36, 39, and 28%, respectively, of initial values. Patients on the placebo preparation showed no significant improvement in ventilatory functions or in the levels of mediators. The findings suggest that the aqueous propolis extract tested is potentially effective as an adjuvant to therapy in asthmatic patients. The benefits may be related to the presence in the extract of caffeic acid derivatives and other active constituents. [source]

    Interactions between TLR7 and TLR9 agonists and receptors regulate innate immune responses by astrocytes and microglia,

    GLIA, Issue 6 2010
    Niranjan B. Butchi
    Abstract Toll-like receptors 7 (TLR7) and 9 (TLR9) are important mediators of innate immune responses. Both receptors are located in endosomal compartments, recognize nucleic acids, and signal via Myeloid differentiation factor 88 (MyD88). In the current study, we analyzed TLR7 and TLR9 induced activation of astrocytes and microglia, two cell types that contribute to innate immune responses in the CNS. TLR7 and TLR9 agonists induced similar cytokine profiles within each cell type. However, there were notable differences in the cytokine profile between astrocytes and microglia, including the production of the anti-inflammatory cytokine IL-10 and antiapoptotic cytokines G-CSF and IL-9 by microglia but not astrocytes. Costimulation studies demonstrated that the TLR7 agonist, imiquimod, could inhibit TLR9 agonist-induced innate immune responses, in both cell types, in a concentration-dependent manner. Surprisingly, this inhibition was not mediated by TLR7, as deficiency in TLR7 did not alter suppression of the TLR9 agonist-induced responses. The suppression of innate immune responses was also not due to an inhibition of TLR9 agonist uptake. This suggested that imiquimod suppression may be a direct effect, possibly by blocking CpG-ODN binding and/or signaling with TLR9, thus limiting cell activation. An antagonistic relationship was also observed between the two receptors in microglia, with TLR7 deficiency resulting in enhanced cytokine responses to CpG-ODN stimulation. Thus, both TLR7 and its agonist can have inhibitory effects on TLR9-induced cytokine responses in glial cells. © 2009 Wiley-Liss, Inc. [source]

    Urea Sensitization Caused by Separation of Helicobacter pylori RNA Polymerase , and ,, Subunits

    HELICOBACTER, Issue 2 2007
    Daiva Dailidiene
    Abstract Background:, The , and ,, subunits of RNA polymerase are fused in all Helicobacters, but separate in most other taxa. Prior studies had shown that this fusion is not essential for viability in culture or in vivo, but had not tested it for potentially important quantitative effects on phenotype. Methods:, The effect of separating rpoB and rpoC sequences on Helicobacter pylori growth was tested in culture and during mouse infection. Results:, Derivatives of strains X47 and SS1 carrying this "rpoBCsplit" allele colonized mice less vigorously than their wild-type parents in competition tests. With X47 rpoBCsplit, this reduced vigor was evident in wild-type mice, whereas with SS1 rpoBCsplit it was seen only in cytokine IL-10- and IL-12,-deficient mice. In culture, the rpoBCsplit allele sensitized each of four strains tested (X47, SS1, 88-3887, and AM1) to urea, a metabolite that is secreted into the gastric mucosa; urea sensitization was more severe in X47 than in SS1 genetic backgrounds. The rpoBCsplit allele also caused poorer growth on Ham's F12 agar, a nutritionally limiting medium, but had little effect on sensitivity to mild acidity. Conclusions:,H. pylori's normal RNA polymerase ,-,, subunit fusion contributes quantitatively to fitness. We propose that urea, although important to H. pylori in vivo, also be considered inhibitory; and that H. pylori's natural ,-,, subunit fusion helps it cope with urea exposure. [source]

    Protein array technology to investigate cytokine production by monocytes from patients with advanced alcoholic cirrhosis: An ex vivo pilot study

    HEPATOLOGY RESEARCH, Issue 7 2009
    Khalid A. Tazi
    Aim:, In patients with advanced cirrhosis, little is known about the ability of peripheral blood monocytes to spontaneously produce signaling proteins such as cytokines. The aim of this ex vivo study was to evaluate cytokine production under baseline conditions and after stimulation by lipopolysaccharide (LPS), a toll-like receptor (TLR) agonist. Methods:, Peripheral blood monocytes were isolated from patients with advanced alcoholic cirrhosis (without ongoing bacterial infections) and normal subjects. Cells were left unstimulated or were stimulated with LPS. The abundance of 24 cytokines was measured using a filter-based, arrayed sandwich enzyme-linked immunosorbent assay (ELISA) in the supernatant of cultured monocytes. Results:, Cirrhotic monocytes spontaneously produced six proteins (TNF-,, IL-6, IL-8, MCP-1, RANTES and Gro), whereas normal monocytes produced only small amounts of IL-8 and RANTES. Analyses with the online gene set analysis toolkit WebGestalt (http://bioinfo.vanderbilt.edu/webgestalt) found enrichment for the six proteins in the human gene ontology subcategory (http://www.geneontology.org), Kyoto Encyclopedia of Genes and Genome pathways (http://www.genome.ad.jp/kegg/) and BioCarta pathways (http://www.biocarta.com/genes/index.asp) consistent with a proinflammatory phenotype of cirrhotic monocytes resulting from activated TLR signaling. Interestingly, LPS-elicited TLR engagement further increased the production of the six proteins and did not induce the secretion of any others, in particular the anti-inflammatory cytokine IL-10. LPS-stimulated normal monocytes produced TNF-,, IL-6, IL-8, MCP-1, RANTES, Gro and IL-10. Conclusion:, In patients with advanced cirrhosis, peripheral blood monocytes spontaneously produce proinflammatory cytokines, presumably in response to unrestricted TLR signaling. [source]

    Defective Toll-like receptor 9-mediated cytokine production in B cells from Bruton's tyrosine kinase-deficient mice

    IMMUNOLOGY, Issue 2 2008
    Maroof Hasan
    Summary Bruton's tyrosine kinase (Btk), a member of the Tec family of tyrosine kinases, plays an important role in the differentiation and activation of B cells. Mutations affecting Btk cause immunodeficiency in both humans and mice. In this study we set out to investigate the potential role of Btk in Toll-like receptor 9 (TLR9) activation and the production of pro-inflammatory cytokines such as interleukin (IL)-6, tumour necrosis factor (TNF)-, and IL-12p40. Our data show that Btk-deficient B cells respond more efficiently to CpG-DNA stimulation, producing significantly higher levels of pro-inflammatory cytokines but lower levels of the inhibitory cytokine IL-10. The quantitative reverse transcription,polymerase chain reaction (RT-PCR) analysis presented in this work shows that mRNA production of one of the important new members of the IL-12 family, IL-27, was significantly increased in Btk-deficient B cells after CpG-DNA stimulation. In this study, we demonstrate significant differences in CpG responsiveness between transitional 1 (T1) and T2 B cells for survival and maturation. Furthermore, TLR9 expression, measured both as protein and as mRNA, was increased in Btk-defective cells, especially after TLR9 stimulation. Collectively, these data provide evidence in support of the theory that Btk regulates both TLR9 activation and expression in mouse splenic B cells. [source]

    Can the brain inhibit inflammation generated in the skin?

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2002
    -melanocyte-stimulating hormone, The lesson of
    The neuro-immuno-cutaneous-endocrine network is not a simple construct featuring organ systems intimately involved in the bridge between body and mind. Mind-body influences are bi-directional and the skin should be considered an active neuroimmunoendocrine interface, where effector molecules of neuropeptides act as common words used in a dynamic dialogue between brain, immune system and skin. Alpha-melanocyte stimulating hormone (,-MSH), one of the principal neuroimmunomodulating peptides, seems to exercise some control on the cutaneous inflammatory process, through a central action mediated by descending anti- inflammatory neural pathways and via local direct influence on inflammatory cells infiltrating the dermis, such as monocytes, macrophages and neutrophils. ,-MSH down-regulates the production of proinflammatory cytokines, while the production of the anti-inflammatory cytokine IL-10 is stimulated by ,-MSH. Finally, ,-MSH seems to regulate the expression of surface molecules in immunocompetent cells. Thus, further studies may lead to the use of ,-MSH as an important anti-inflammatory agent in clinical dermatology. [source]

    Inhibition of the p38 pathway upregulates macrophage JNK and ERK activities, and the ERK, JNK, and p38 MAP kinase pathways are reprogrammed during differentiation of the murine myeloid M1 cell line

    JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2002
    J. Perry Hall
    Abstract Mitogen-activated protein (MAP) kinases have been implicated as important mediators of the inflammatory response. Here we report that c-Jun NH2 -terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 MAP kinase activities are reprogrammed during the IL-6 induced macrophage-like differentiation of the murine myeloid M1 cell line. Moreover, p38 inhibition upregulates JNK and ERK activity in M1 cells and in thioglycollate-elicited peritoneal exudate macrophages. IL-6-induced M1 differentiation also induces expression of the anti-inflammatory cytokine IL-10, and p38 inhibition potentiates this increase in IL-10 expression in an ERK-dependent manner. Thus, we speculate that during inflammatory conditions in vivo macrophage p38 may regulate JNK and ERK activity and inhibit IL-10 expression. These data highlight the importance of p38 in the molecular mechanisms of macrophage function. J. Cell. Biochem. 86: 1,11, 2002. © 2002 Wiley-Liss, Inc. [source]

    Anti-inflammatory effects of continuous passive motion on meniscal fibrocartilage

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2005
    Mario Ferretti
    Abstract Motion-based therapies have been applied to promote healing of arthritic joints. The goal of the current study was to determine the early molecular events that are responsible for the beneficial actions of motion-based therapies on meniscal fibrocartilage. Rabbit knees with Antigen-Induced-Arthritis (AIA) were exposed to continuous passive motion (CPM) for 24 or 48 h and compared to immobilized knees. The menisci were harvested and glycosaminoglycans (GAG), interleukin-1, (IL-1,), matrix metalloproteinase-1 (MMP-1), cyclooxygenase-2 (COX-2), and interleukin-10 (IL-10) were determined by histochemical analysis. Within 24 h, immobilized knees exhibited marked GAG degradation. The expression of proinflammatory mediators MMP-1, COX-2, and IL-1, was notably increased within 24 h and continued to increase during the next 24 h in immobilized knees. Knees subjected to CPM revealed a rapid and sustained decrease in GAG degradation and the expression of all proinflammatory mediators during the entire period of CPM treatment. More importantly, CPM induced synthesis of the anti-inflammatory cytokine IL-10. The results demonstrate that mechanical signals generated by CPM exert potent anti-inflammatory signals on meniscal fibrochondrocytes. Furthermore, these studies explain the molecular basis of the beneficial effects of CPM observed on articular cartilage and suggest that CPM suppresses the inflammatory process of arthritis more efficiently than immobilization. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source]

    Counter regulation of the high affinity IgE receptor, Fc,RI, on human airway dendritic cells by IL-4 and IL-10

    ALLERGY, Issue 11 2009
    A. Faith
    Background:, Immunoglobulin E is a signalling molecule within the environment of the respiratory tract, the high affinity receptor for which, Fc,RI, is expressed by dendritic cells (DC). Little is known, however, of the expression and function of Fc,RI on DC in the human respiratory tract. Methods:, CD1c+ DC were purified from surgically resected nasal turbinates of 11 atopic and 12 nonatopic patients with chronic rhinosinusitis. Expression of Fc,RI was determined by flow cytometry. Cytokine production by DC was determined by cytometric bead array. Results:, Expression of Fc,RI was significantly elevated on respiratory tract dendritic cells (RTDC) from atopic as compared to nonatopic patients. Activation of RTDC through Fc,RI induced production of the pro-inflammatory cytokines IL-6 and TNF-,, and the anti-inflammatory cytokine IL-10. The production of IL-6 and TNF-, was elevated in atopic compared to nonatopic patients studied. Conversely IL-10 production was elevated in nonatopic patients. Concomitant activation of Fc,RI and stimulation of RTDC with IL-4 inhibited production of IL-10 by RTDC. Neutralization experiments with anti-IL-10 Ab enhanced whereas addition of exogenous IL-10 to RTDC inhibited Fc,RI-mediated inflammatory cytokine production. Conclusion:, The function of Fc,RI on RTDC from patients with rhinosinusitis is susceptible to counter regulation by IL-4 and IL-10. [source]

    Antimicrobial and anti-inflammatory activity of five Taxandria fragrans oils in vitro

    MICROBIOLOGY AND IMMUNOLOGY, Issue 11 2008
    Katherine A. Hammer
    ABSTRACT The antimicrobial activity of five samples of Taxandria fragrans essential oil was evaluated against a range of Gram-positive (n= 26) and Gram-negative bacteria (n= 39) and yeasts (n= 10). The majority of organisms were inhibited and/or killed at concentrations ranging from 0.06,4.0% v/v. Geometric means of MIC were lowest for oil Z (0.77% v/v), followed by oils X (0.86%), C (1.12%), A (1.23%) and B (1.24%). Despite differences in susceptibility data between oils, oils A and X did not differ when tested at 2% v/v in a time kill assay against Staphylococcus aureus. Cytotoxicity assays using peripheral blood mononuclear cells demonstrated that T. fragrans oil was cytotoxic at 0.004% v/v but not at 0.002%. Exposure to one or more of the oils at concentrations of ,0.002% v/v resulted in a dose responsive reduction in the production of proinflammatory cytokines IL-6 and TNF-,, regulatory cytokine IL-10, Th1 cytokine IFN-, and Th2 cytokines IL-5 and IL-13 by PHA stimulated mononuclear cells. Oil B inhibited the production of all cytokines except IL-10, oil X inhibited TNF-,, IL-6 and IL-10, oil A inhibited TNF-, and IL-6, oil C inhibited IL-5 and IL-6 and oil Z inhibited IL-13 only. IL-6 production was significantly inhibited by the most oils (A, B, C and X), followed by TNF-, (oils A, B and X). In conclusion, T. fragrans oil showed both antimicrobial and anti-inflammatory activity in vitro, however, the clinical relevance of this remains to be determined. [source]

    Radiation Sources Providing Increased UVNUVB Ratios Induce Photoprotection Dependent on the UVA Dose in Hairless Mice

    PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2006
    Vivienne E. Reeve
    ABSTRACT In studies involving mice in which doses of UVA (320,400 nm) and UVB (290,320 nm) radiation were administered alone or combined sequentially, we observed a protective effect of UVA against UVB-induced erythemdedema and systemic suppression of contact hypersensitivity. The UVA immunoprotection was mediated by the induction of the stress enzyme heme oxygenase-1 (HO-1) in the skin, protection of the cutaneous Th1 cytokines interferon-gM (IFN-,) and IL-12 and inhibition of the UVB-induced expression of the Th2 cytokine IL-10. In this study, we seek evidence for an immunological waveband interaction when UVA and UVB are administered concurrently to hairless mice as occurs during sunlight exposure in humans. A series of spectra providing varying ratios of UVA/UVB were developed, with the UVA ratio increased to approximately 3.5 times the UVA component in solar simulated UV (SSUV). We report that progressively increasing the UVA component of the radiation while maintaining a constant UVB dose resulted in a reduction of both the erythemdedema reaction and the degree of systemic immunosuppression, as measured as contact hypersensitivity. The UVA-enhanced immunoprotection was abrogated in mice treated with a specific HO enzyme inhibitor. UVA-enhanced radiation also upregulated the expression of cutaneous IFN-, and IL-12 and inhibited expression of both IL-6 and IL-10, compared with the activity of SSUV. The results were consistent with the previously characterized mechanisms of photoprotection by the UVA waveband alone and suggest that the UVA component of solar UV may have beneficial properties for humans. [source]

    Dendritic cells lentivirally engineered to overexpress interleukin-10 inhibit contact hypersensitivity responses, despite their partial activation induced by transduction-associated physical stress

    THE JOURNAL OF GENE MEDICINE, Issue 3 2010
    Verena Besche
    Abstract Background Dendritic cells (DCs) constitute an attractive target for immunotherapeutic approaches. Because DCs are largely refractory to transfection with plasmid DNA, several viral transduction protocols were established. The potential side-effects of lentiviral transduction on the phenotype and activation state of DCs left unstimulated after transduction have not been assessed. There is a need to analyse these parameters as a result of the requirement of using DCs with a low activation state for therapeutic strategies intended to induce tolerance. Methods Lentivirally-transduced bone marrow (BM)-derived DCs (LV-DCs) in comparison with mock-transduced (Mock-DCs) and untreated DCs were analysed with regard to the induction of maturation processes on the RNA, protein and functional level. BM-DCs engineered to overexpress interleukin (IL)-10 were analysed for therapeutic potential in a mouse model of allergic contact dermatitis. Results Compared with untreated DCs, Mock-DCs and LV-DCs displayed an altered gene expression signature. Mock-DCs induced a stronger T cell proliferative response than untreated DCs. LV-DCs did not further augment the T cell proliferative response, but induced a slightly different T cell cytokine pattern compared to Mock-DCs. Accordingly, the gene promoter of the DC maturation marker fascin mediated efficient expression of the model transgene IL-10 in unstimulated-transduced BM-DCs. Nevertheless, IL-10 overexpressing BM-DCs exerted tolerogenic activity and efficiently inhibited the contact hypersensitivity response in previously hapten-sensitized mice. Conclusions Lentiviral transduction of BM-DCs results in their partial activation. Nevertheless, the transduction of these DCs with a vector encoding the immunomodulatory cytokine IL-10 rendered them tolerogenic. Thus, lentivirally-transduced DCs expressing immunomodulatory molecules represent a promising tool for induction of tolerance. Copyright © 2010 John Wiley & Sons, Ltd. [source]

    IL-10 and the resolution of infections,

    THE JOURNAL OF PATHOLOGY, Issue 2 2008
    CM Filippi
    Abstract Chronic viral infections pose serious health concerns, as secondary complications such as immunodeficiencies and cancers are common. Treating such infections with conventional vaccine approaches has proved to be difficult. Studies in animals and humans suggest that vaccine failure is probably due to exhaustion of antiviral T cell responses, which occurs in a number of chronic infections. Attempts to elucidate the causes of impairment of antiviral immunity have pointed to a role for the immunomodulatory cytokine IL-10 in the ability of viruses to establish persistence. Induction of IL-10 production by the host during chronic infection appears to be one of the viral means to alter the class of the antiviral immune response and induce generalized immune suppression. Recent work by us and others suggests that it is possible to resuscitate antiviral immunity by interfering with the IL-10 signalling pathway. Targeting IL-10 thus constitutes a promising alternative to conventional vaccine strategies which have not proved to be successful in treating chronic infections. In addition, sterile cure may be achieved with minimal side-effects by combining agents that alter the IL-10 signalling pathway with other compounds, such as antiviral drugs or interferon, but also agents neutralizing other crucial elements of T cell exhaustion, such as PD-1. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

    The Multifunctional Role of mTOR in Innate Immunity: Implications for Transplant Immunity

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009
    M. D. Säemann
    The mammalian target of rapamycin (mTOR) is an evolutionary conserved serine,threonine kinase that senses various environmental stimuli in most cells primarily to control cell growth. Restriction of cellular proliferation by mTOR inhibition led to the use of mTOR inhibitors as immunosuppressants in allogeneic transplantation as well as novel anticancer agents. However, distinct inflammatory side effects such as fever, pneumonitis, glomerulonephritis or anemia of chronic disease have been observed under this treatment regime. Apart from the mere cell-cycle regulatory effect of mTOR in dividing cells, recent data revealed a master regulatory role of mTOR in the innate immune system. Hence, inhibition of mTOR promotes proinflammatory cytokines such as IL-12 and IL-1,, inhibits the anti-inflammatory cytokine IL-10 and boosts MHC antigen presentation via autophagy in monocytes/macrophages and dendritic cells. Moreover, mTOR regulates type I interferon production and the expression of chemokine receptors and costimulatory molecules. These results place mTOR in a complex immunoregulatory context by controlling innate and adaptive immune responses. In this review, we discuss the clinical consequences of mTOR-inhibitor therapy and aim to integrate this recent data into our current view of the molecular mechanisms of clinically employed mTOR inhibitors and discuss their relevance with special emphasis to transplantation. [source]

    Intra-tumoral interleukin-6 down-regulation system and genetic mutations of tumor suppressor genes in colorectal carcinoma

    CANCER, Issue 5 2002
    Chikao Miki M.D.
    Abstract BACKGROUND The interleukin (IL)-1-IL-6 network, the most potent cascade of pro-inflammatory cytokines, plays an autocrine role in tumor growth. The IL-1-IL-6 network is down-regulated by a phased cytokine inhibitor IL-1 receptor antagonist (ra) and an anti-inflammatory cytokine IL-10. The current study evaluated this down-regulation system in colorectal carcinoma and its relation to the genetic alteration of tumor suppressor genes. METHODS Seventy-four specimens of primary colorectal carcinoma and normal mucosa were collected to measure tissue concentrations of cytokines. Polymerase chain reaction amplification was performed to investigate the loss of heterozygosity of the microsatellite markers on chromosomes 17p and 18q. RESULTS The IL-1ra/IL-6 ratio in the carcinoma specimens was lower than ratios in adenomas and normal mucosae and decreased with disease progression. The IL-1ra/IL-6 ratio in early cancers tended to be lower than that in adenomas and normal mucosae. However, the tissue concentrations of IL-1, and IL-10 were not associated with any clinicopathologic parameters. The tissue IL-1ra concentration correlated with that of IL-6 only in adenomas and early cancers. Immunohistochemically, IL-1ra and IL-6 were localized in the tumor cytoplasm. A reduced tissue IL-1ra/IL-6 ratio in the carcinomas correlated with poor prognosis and was associated with the loss of heterozygosity of the microsatellite markers on chromosomes 18q. CONCLUSIONS There is an IL-6-IL-1ra network system in colorectal tumors, but this system deteriorates with carcinogenesis and tumor growth. The deterioration of this network system was associated with the allelic loss of a portion of chromosome 18q, reflecting the genetic alteration of tumor suppressor genes. Cancer 2002;94:1584,92. © 2002 American Cancer Society. DOI 10.1002/cncr.10324 [source]

    Immunoreactivity profile of peripheral blood mononuclear cells from patients with ragweed-induced allergic rhinitis

    CLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2007
    J. Sun
    Summary Background Seasonal rhinitis is manifested by a series of nasal symptoms in response to exposure to seasonal allergens including ragweed pollen. Understanding its immunological mechanisms may help to better manage the disease. Objective We sought to determine comprehensively ragweed-induced cytokine and chemokine production by peripheral blood mononuclear cells from normal individuals and patients with seasonal rhinitis sensitized to ragweed pollen, and to assess its regulation by exogenous IL-10. Methods Cells were cultured in the presence or absence of a purified ragweed pollen extract with or without exogenous IL-10. Cytokines and chemokines were measured in the supernatant. Gene expression was evaluated using real-time quantitative reverse transcription PCR. Results Ragweed stimulation significantly increased the production of the Th2-associated cytokines IL-5, IL-9 and IL-13, the chemokines CCL17 and CCL22 and the regulatory cytokine IL-10 in allergic patients, whereas transforming growth factor-, (TGF-,) production was increased only in normal individuals. No difference was detected between groups in the production of the Th1 cytokine IFN-, or the Th1-affiliated chemokines CXCL10 and CXCL11. Exogenous IL-10 significantly suppressed spontaneous and induced production of both Th1- and Th2-associated cytokines and chemokines. Conclusion Our work demonstrated that locally manifested allergic rhinitis is underlined by a systemic Th2 immune response specific to allergens. The molecular pathogenesis of allergic rhinitis may be linked to a compromised allergen-specific immune regulation, e.g., reduced spontaneous and allergen-induced TGF-, production in patients compared with healthy controls. Our data also show that IL-10 inhibits both the effector and directional mechanisms of allergen-specific immune response, further supporting its potential therapeutic benefit in preventing and treating allergic diseases. [source]

    Dominant IL-10 and TGF-, mRNA Expression in ,,T Cells of Human Early Pregnancy Decidua Suggests Immunoregulatory Potential

    AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2002
    OLGA NAGAEVA
    PROBLEM:,To examine the cytokine gene expression in ,,T-cells from human early pregnancy decidua. METHOD OF STUDY:,The cytokine messenger RNA (mRNA) expression in isolated decidual T-cell receptor (TCR),,+/CD56+ and TCR,, single positive cells was investigated with a panel of cytokine primers and probes selected to distinguish between T helper (Th)1, Th2, Th3 and regulatory T-cells (Tr1) type of immune response using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS:,TCR,,+/CD56+ cells express almost exclusively the immunosuppressive cytokines interleukin-10 (IL-10) and transforming growth factor (TGF)-,. The TCR,, single positive cells enhance their transcription of IL-10 and TGF-,, compared with the TCR,,+/CD56+ cells and additionally express mRNA for IL-1, and IL-6. CONCLUSIONS:,The present findings suggest that ,,T cells in normal pregnancy create a cytokine milieu promoting immunotolerance to the fetus. We hypothesize that through the production of the immunosuppressive cytokines IL-10 and/or TGF-, the ,,T cells could function directly as regulatory T cells or induce the differentiation of Th0 TCR,,+ cells into regulatory/suppresser cells. [source]

    Immunomodulatory properties of human serum immunoglobulin A: anti-inflammatory and pro-inflammatory activities in human monocytes and peripheral blood mononuclear cells

    CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005
    K. Olas
    Summary Our study investigated the immunomodulatory activities of human plasma-derived serum immunoglobulin (Ig)A. Previous findings seem contradictory indicating either pro- or anti-inflammatory activities. We used serum IgA purified from large plasma pools and studied the modulation of the release of cytokines and chemokines from resting and lipopolysaccharide (LPS, endotoxin)-stimulated human adherent monocytes and human peripheral blood mononuclear cells (PBMC). Our results indicate that IgA down-modulates the release of the pro-inflammatory chemokines monocyte chemoattractant protein (MCP) 1, macrophage inflammatory protein (MIP) 1, and MIP1, from LPS-stimulated PBMC and the release of MCP1, MIP1, and MIP1, from LPS-stimulated monocytes. Furthermore, we confirmed previous reports that plasma-derived serum IgA down-modulates the release of the pro-inflammatory cytokines, interleukin (IL)-6 and tumour necrosis factor (TNF)-,, from LPS-stimulated monocytes and PBMC, and up-regulates the release of IL-1 receptor antagonist (IL-1RA) from resting and LPS-stimulated monocytes and resting PBMC. This IgA-mediated up-regulation of IL-1RA is independent of the simultaneous up-regulation of IL-1, release, as shown by blocking the biological activity of IL-1, with a neutralizing antibody. On the other hand, we also found an IgA-induced pro-inflammatory activity, namely IgA-mediated up-regutation of the release of pro-inflammatory IL-1, as well as down-regulation of the anti-inflammatory cytokines IL-10 and IL-12p40 from LPS-stimulated monocytes and PBMC and a down-regulation of transforming growth factor (TGF)-, from resting and LPS-stimulated PBMC. We conclude that human serum IgA has both an anti-inflammatory and a pro-inflammatory capacity and this dual capacity might contribute to the feedback mechanisms maintaining a balance between pro-inflammatory and anti-inflammatory activities. [source]

    Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN- ,, IL-4, IL-10 and IL-13) in patients with allergic asthma

    CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2001
    C. K. Wong
    Allergen-reactive T helper type-2 (Th2) cells and proinflammatory cytokines have been suggested to play an important role in the induction and maintenance of the inflammatory cascade in allergic asthma. We compared the plasma concentrations of novel proinflammatory cytokines IL-17 and IL-18, other proinflammatory cytokines IL-6 and IL-12, Th2 cytokines IL-10 and IL-13, and intracellular interferon- , (IFN- ,) and IL-4 in Th cells of 41 allergic asthmatics and 30 sex- and age-matched health control subjects. Plasma cytokines were measured by enzyme-linked immunosorbent assay. Intracellular cytokines were quantified by flow cytometry. Plasma IL-18, IL-12, IL-10, IL-13 concentrations were significantly higher in allergic asthmatic patients than normal control subjects (IL-18: median 228·35 versus 138·72 pg/ml, P < 0·001; IL-12: 0·00 versus 0·00 pg/ml, P = 0·001; IL-10: 2·51 versus 0·05 pg/ml, P < 0·034; IL-13: 119·38 versus 17·89 pg/ml, P < 0·001). Allergic asthmatic patients showed higher plasma IL-17 and IL-6 concentrations than normal controls (22·40 versus 11·86 pg/ml and 3·42 versus 0·61 pg/ml, respectively), although the differences were not statistically significant (P = 0·077 and 0·053, respectively). The percentage of IFN- , -producing Th cells was significantly higher in normal control subjects than asthmatic patients (23·46 versus 5·72%, P < 0·001) but the percentage of IL-4 producing Th cells did not differ (0·72 versus 0·79%, P > 0·05). Consequently, the Th1/Th2 cell ratio was significantly higher in normal subjects than asthmatic patients (29·6 versus 8·38%, P < 0·001). We propose that allergic asthma is characterized by an elevation of both proinflammatory and Th2 cytokines. The significantly lower ratio of Th1/Th2 cells confirms a predominance of Th2 cells response in allergic asthma. [source]