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Tissue Inflammation (tissue + inflammation)

Distribution by Scientific Domains
Medical Sciences95%
Distribution within Medical Sciences
Implant Dentistry13%
Allergy & Clinical Immunology8%
11 Other Subdomains53%

Kinds of Tissue Inflammation

  • soft tissue inflammation
    		•

    Selected Abstracts

    Prednisone Prevents Inducible Atrial Flutter in the Canine Sterile Pericarditis Model

    JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2008
    ROBERT N. GOLDSTEIN M.D.
    Background: Atrial fibrillation (AF) and atrial flutter (AFL) are common following cardiac surgery and are associated with significant morbidity. We tested the hypothesis that suppression of the inflammatory response with steroids would significantly modify the inducibility of postoperative AF/AFL in the canine sterile pericarditis model. Methods: Twenty-three dogs were studied daily from creation of pericarditis to the fourth postoperative day: 11 dogs were treated with oral prednisone (PRED) starting 2 days preoperatively until the end of the study; 12 dogs were controls (CON). EP testing was performed daily using epicardial electrodes placed at initial surgery. High-resolution (404 sites) epicardial mapping was performed during the terminal study. Baseline and daily CRP levels were obtained in all dogs. Results: Sustained AFL was absent in PRED (0%) versus CON dogs (91%; P < 0.001); AF induced in the early postoperative course in PRED dogs was of very short CL (mean 66 ms). Tissue inflammation was significantly attenuated in PRED dogs. Thresholds were lower in PRED versus CON dogs, significantly so on postoperative day (POD) 3. There was a trend toward lower ERPs in the PRED group at all CLs. CRP levels were markedly reduced in PRED versus CON dogs (peak CRP 78 ± 7 mg/L vs 231 ± 21 mg/L, P < 0.001), and returned to baseline in PRED dogs by POD 4, correlating with a virtual absence of sustained arrhythmia. During open chest mapping studies on POD 4, PRED dogs showed only nonsustained AF/AFL. Conclusions: Prednisone eliminated postoperative AFL, affected all EP parameters studied, and attenuated the inflammatory response associated with pericarditis. [source]

    IL-23-driven encephalo-tropism and Th17 polarization during CNS-inflammation in vivo

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2009
    Gabor Gyülvészi
    Abstract IL-23 but not IL-12 is essential for the development of autoimmune tissue inflammation in mice. Conversely, IL-12 and IL-23 impact on the polarization of Th1 and Th17 cells, respectively. While both polarized T helper populations can mediate autoimmune inflammation, their redundancy in the pathogenesis of EAE indicates that IL-23 exerts its crucial influence on the disease independent of its T helper polarizing capacity. To study the impact of IL-23 and IL-12 on the behavior of encephalitogenic T cells in vivo, we generated BM-chimeric mice in which we can trace individual populations of IL-23 or IL-12 responsive T helper cells during EAE. We observed that T cells, which lack IL-12R,1 (no IL-12 and IL-23 signaling), fail to invade the CNS and do not acquire a Th17 phenotype. In contrast, loss of IL-12 signaling prevents Th1 polarization but does not prevent T-cell entry into the CNS. The loss of IL-12R engagement does not appear to alter T-cell expansion but leads to their accumulation in secondary lymphoid organs. We found that IL-23 licenses T cells to invade the target tissue and to exert their effector function, whereas IL-12 is critical for Th1 differentiation, but does not influence the pathogenic capacity of auto-reactive T helper cells in vivo. [source]

    Adipokines in liver diseases,

    HEPATOLOGY, Issue 3 2009
    Fabio Marra
    Adipokines are polypeptides secreted in the adipose tissue in a regulated manner. While some of these molecules are expressed only by adipocytes, resident and infiltrating macrophages and components of the vascular stroma markedly contribute to expression of other adipokines. As a result, adipose tissue inflammation is associated with a modification in the pattern of adipokine secretion. Leptin, adiponectin, and resistin are the best-studied molecules in this class, but cytokines such as tumor necrosis factor or interleukin-6 are also secreted at high levels by the adipose tissue. Several other molecules have been recently identified and are actively investigated. Adipokines interfere with hepatic injury associated with fatty infiltration, differentially modulating steatosis, inflammation, and fibrosis. Several studies have investigated plasma levels of adiponectin in patients with nonalcoholic fatty liver disease, to establish correlations with the underlying state of insulin resistance and with the type and severity of hepatic damage. Hepatitis C is another disease where adipokines may represent a link between viral infection, steatosis, and metabolic disturbances. Identification of the mediators secreted by expanded adipose tissue and their pathogenic role is pivotal in consideration of the alarming increase in the prevalence of obesity and of the detrimental role that this condition exerts on the course of liver diseases. (HEPATOLOGY 2009.) [source]

    Therapeutic benefit of pentostatin in severe IL-10,/, Colitis

    INFLAMMATORY BOWEL DISEASES, Issue 7 2008
    Jeffrey B. Brown MD
    Abstract Background: Pentostatin, an adenosine deaminase (ADA) inhibitor, is a purine antimetabolite used for the treatment of leukemias. ADA inhibition blunts expansion of proliferating lymphocytes and increases adenosine release, a potent anti-inflammatory molecule. Human inflammatory bowel disease (IBD) is driven by expansion of effector T cells (Teff) that overwhelm reulatory T cells (Treg) and propagate innate immune reponses. Here we study the therapeutic benefits of ADA inhibition to impair Teff cell expansion and reduce inflammatory cytokine release in IL-10-deficient (IL-10 -/- ) mice. Methods: Colitis was induced in IL-10 -/- mice by administering piroxicam for two weeks. Mice were treated with daily pentostatin or phosphate-buffered saline for 1 week and effects on tissue inflammation, lymphocyte numbers and cytokine production examined. Results: Pentostatin reduced inflammation by >50% and nearly normalized serum amyloid A levels. Lymphocyte expansions in the colon and mesenteric lymph node (MLN) (3.5-fold and >5-fold respectively) dropped by >50-90%. Pro-inflammatory factors in the colon and MLN (IL-1,, IFN-,, IL-6, CXCL10, TNF) dropped whereas FoxP3 and TGF-, were unchanged. Reductions in cytokine production from equivalent numbers of T cells from pentostatin-treated mice after in vitro (36h) or in vivo (3h) activation suggested anti-inflammatory effects of pentostatin independent of lymphodepletion contributed to its therapeutic benefit. Analysis of mucosal lymphocyte subsets suggested pentostatin reduced numbers of effector CD4+ CD69+ T cells, while sparing CD4+ CD62L+ T cells. Conclusions: Pentostatin dosages that avoid severe lymphocyte depletion effectively treat colitis by impairing Teff cell expansion and reducing pro-inflammatory cytokine production while preserving regulatory Treg populations and function. (Inflamm Bowel Dis 2008) [source]

    Immunohistochemical characteristics of inflammatory lesions at implants

    JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 1 2003
    Federico Gualini
    Abstract Objective: The aim of the present investigation was to study some immunohistochemical features of peri-implant mucositis and peri-implantitis lesions. Materials and methods: Two groups of subjects (Groups A and B) were included. Group A consisted of 10 partially edentulous subjects (eight females and two males; 45,72 years of age) who had been restored with implants (Brånemark System®, Nobel Biocare AB, Göteborg, Sweden). The implants had been in function between 2 and 5 years. In each subject, one implant site demonstrating signs of peri-implant mucositis, i.e. soft tissue inflammation but no bone loss, was selected. The site was anaesthetized and a soft tissue biopsy was collected. In Group B, six subjects were included. They had been restored with implants (Brånemark System®, Nobel Biocare AB, Göteborg, Sweden) between 5 and 11 years prior to the current study. In each individual ,,1 implant site exhibited signs of peri-implantitis and was selected for biopsy. All sites of peri-implantitis had (i) a history of continuous marginal bone loss (assessed in radiographs), (ii) clinical symptoms of soft tissue inflammation (bleeding on probing and suppuration) but (iii) no implant mobility. From each selected peri-implantitis site a 4 × 4 mm large soft tissue biopsy was obtained. All specimens were snap frozen and prepared for immunohistochemical analysis regarding the proportions of cells positive for the CD3, CD4, CD8, CD19 and elastase markers. Results: Peri-implantitis lesions were considerably larger and contained significantly greater proportions of B cells (CD19+) and elastase-positive cells than mucositis lesions. Peri-implantitis sites, in contrast to sites with mucositis, consistently displayed elastase-positive cells in the central portions of the infiltrate. Conclusion: It is suggested that peri-implantitis lesions exhibit properties that are different from mucositis lesions. [source]

    Relative effectiveness of powered and manual toothbrushes in elderly patients with implant-supported mandibular overdentures

    JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2002
    A. Tawse-Smith
    Abstract Aim: The aim of this study was to compare the clinical effectiveness of a powered toothbrush (Braun Oral-B Plaque Remover 3-D) and a manual soft toothbrush (Oral-B Squish-grip brush) for the control of supragingival plaque and soft tissue inflammation around implants supporting mandibular overdentures. Material and methods: The study sample involved 40 edentulous subjects, aged 55,80 years, having 2 unsplinted mandibular implants supporting a complete removable overdenture opposed by a maxillary complete denture. In this single-blinded, randomised, cross-over clinical trial, two 6-week experimental phases were separated by a 2-week wash-out period. 2 weeks prior to each experimental phase (pre-entry visits), implant abutments were polished to remove all plaque and a standardised instruction in the use of the toothbrush was given. Modified plaque and bleeding indices were recorded at the start and end of each experimental period. Mean index scores at each phase were analysed using paired t -test, and the mean number of sites showing a change in plaque or mucositis were compared using the Mann-Whitney U -test. Combined data from 2 different implant systems were considered after controlling for implant type. Results: Only minor changes in plaque and bleeding scores were observed following the two test periods. There were no statistically significant differences between the manual and powered toothbrushes. Conclusion: Manual and powered brushes were found to be of comparable efficacy with regard to improvement in peri-implant bleeding and plaque indices. Zusammenfassung Zielsetzung: Untersuchung der klinischen Effektivität einer elektrischen Zahnbürste (Braun Oral-B Plaque Remover 3-D) im Vergleich zu einer weichen Handzahnbürste (Oral-B Squish-grip brush) zur Kontrolle supragingivaler Plaque und Weichgewebsentzündung an Implantaten, die Unterkiefer-Totalprothesen tragen. Material und Methoden: Das Untersuchungskollektiv bestand aus 40 zahnlosen Patienten im Alter zwischen 55 und 80 Jahren, die 2 unverblockte Unterkiefer-Implantate zur Unterstützung einer Totalprothese aufwiesen. Der Oberkiefer war jeweils mit einer total schleimhautgetragenen Prothese versorgt. In dieser einfach verblindeten, randomisierten klinischen Cross-over-Studie wurden 2 6-wöchige experimentelle Phasen von einer 2-wöchigen Auswaschperiode unterbrochen. 2 Wochen vor jeder experimentellen Phase wurden die supragingivalen Implantatflächen von sämtlicher Plaque gereinigt und die Patienten erhielten eine Instruktion im Gebrauch der Zahnbürsten. Modifizierte Plaque- und Blutungsindizes wurden zu Beginn und am Ende jeder experimentellen Phase erhoben. Die Mittelwerte für die Indizes wurden mittels des paarigen t -Tests und die Zahl der Stellen, die eine Veränderung in Plaque und Mucositis aufwiesen, wurden durch den Mann-Whitney U -Test verglichen. Die Daten für 2 Implantatsysteme wurden zusammengefasst, nachdem der Einfluss des Implantatsystems überprüft worden war. Ergebnisse: Es wurden nur geringe Veränderungen der Plaque- und Blutungsindizes am Ende beider Testphasen beobachtet. Ein statistisch signifikanter Unterschied zwischen elektrischer und Handzahnbürste konnte nicht gezeigt werden. Schlussfolgerungen: Hand- und elektrische Zahnbürsten erwiesen sich als gleich effektiv für die Verbesserung periimplantärer Plaque- und Blutungsindizes. Résumé But: Le but de cette étude était de comparer l'efficacité clinique d'une brosse à dent électrique (Plaque remover 3D de Braun Oral B) et une brosse souple manuelle (squish grip d'oral B) pour le contrôle de la plaque supra-gingivale et l'inflammation des tissus mous autour d'implants supportant des overdentures mandibulaires. Matériaux et méthodes: L'échantillon étudié comprenait 40 sujets édentés, âgés de 55 à 80 ans, ayant 2 implants mandibulaires non reliés supportant une overdenture amovible complète et une prothèse maxillaire antagoniste complète. Dans cet essai clinique croisé en aveugle simple, randomisée, 2 phases expérimentales de 6 semaines encadraient une période d'arrêt de 2 semaines. 2 semaines avant chaque phase expérimentale, (visite de pré-entrée), les piliers implantaires étaient polis afin d'éliminer toute la plaque et des instructions standardisées d'utilisation de la brosse étaient données. On notait les indices, de saignement et de plaque modifié, au début et à la fin de chaque période expérimentale. Les notes d'indices moyens à chaque phase étaient analysées par le test t apparié et le nombre moyen de sites présentant une modification de la plaque ou de la mucosite était comparé par le test U de Mann Whitney. Les données combinées des 2 systèmes implantaires étaient considérées après cotrôle pour chaque type d'implant Résultats: De minimes modifications des notes de plaque et de saignement étaient observées après les deux périodes de test. Il n'y avait pas de différences statistiques significatives entre les brosses manuelles et électriques. Conclusion: Les brosses manuelles et électriques ont une efficacité comparable du point de vue de l'amélioration des indices de saignement et de plaque peri-implantaires. [source]

    Expression of periodontal interleukin-6 protein is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases

    JOURNAL OF PERIODONTAL RESEARCH, Issue 5 2010
    J. H. Ross
    Ross JH, Hardy DC, Schuyler CA, Slate EH, Mize TW, Huang Y. Expression of periodontal interleukin-6 protein is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases. J Periodont Res 2010; 45: 688,694. © 2010 John Wiley & Sons A/S Background and Objective:, Epidemiological studies have established that patients with diabetes have an increased prevalence and severity of periodontal disease. Interleukin (IL)-6, a multifunctional cytokine, plays a role in the tissue inflammation that characterizes periodontal disease. Our recent study has shown a trend of increase in periodontal IL-6 expression at the mRNA level across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases. However, the periodontal IL-6 expression at the protein level in these patients has not been investigated. Material and Methods:, Periodontal tissue specimens were collected from eight patients without periodontal disease and diabetes (group 1), from 17 patients with periodontal disease alone (group 2) and from 10 patients with both periodontal disease and diabetes (group 3). The frozen sections were prepared from these tissue specimens and IL-6 protein expression was detected and quantified. Results:, The nonparametric Kruskal,Wallis test showed that the difference in IL-6 protein levels among the three groups was statistically significant (p = 0.035). Nonparametric analysis using the Jonckheere,Terpstra test showed a tendency of increase in periodontal IL-6 protein levels across group 1 to group 2 to group 3 (p = 0.006). Parametric analysis of variance (ANOVA) on IL-6 protein levels showed that neither age nor gender significantly affected the difference of IL-6 levels among the groups. Conclusion:, Periodontal IL-6 expression at the protein level is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases. [source]

    The role of eosinophil major basic protein in angiogenesis

    ALLERGY, Issue 3 2009
    I. Puxeddu
    Background:, Eosinophil-derived major basic protein (MBP) plays an active role in allergic inflammation and tissue remodelling. However, its role in angiogenesis has not been established as yet. Therefore our objective was to investigate whether MBP exhibits any direct pro-angiogenic effects. Methods:, Rat aortic endothelial cells and human umbilical vascular endothelial cells were cultured with different concentrations of MBP and their viability (Trypan blue exclusion test), proliferation (thymidine incorporation) and capillary-like structure formation (matrigel assay) were investigated in vitro. The angiogenic activity of MBP was then tested in vivo using the chick chorio allantoic membrane (CAM) assay. Results:, Subcytotoxic concentrations of MBP induce endothelial cell proliferation and enhance the pro-mitogenic effect of vascular endothelial growth factor (VEGF), but do not affect their VEGF release. MBP promotes capillarogenesis by endothelial cells seeded on matrigel and sprouting formation in the CAM assay. Furthermore, we have shown that the pro-angiogenic effect of MBP is not due to its cationic charge since stimulation of the CAMs with the synthetic polycation, poly- l -arginine does not induce any angiogenic effects. Conclusions:, These data demonstrate that MBP has pro-angiogenic effects in vitro and in vivo, providing a novel mechanism whereby MBP can participate in tissue inflammation and remodelling in atopic diseases. [source]

    Omega-3 fatty acid regulates inflammatory cytokine/mediator messenger RNA expression in Porphyromonas gingivalis -induced experimental periodontal disease

    MOLECULAR ORAL MICROBIOLOGY, Issue 4 2007
    L. Kesavalu
    Introduction:,Porphyromonas gingivalis is strongly implicated in the etiology of adult periodontitis by inducing inflammatory cytokines, resulting in gingival and periodontal tissue inflammation and alveolar bone resorption. This study tested the hypothesis that supplementing the diet with omega-3 fatty acid (,-3 FA; i.e. fish oil) would exert anti-inflammatory effects in the gingival tissues of P. gingivalis -infected rats. Methods:, Rats were fed either fish oil or corn oil diets ad libitum for 22 weeks and infected with P. gingivalis strain 381 or strain A7A1-28. After sacrifice, rat gingival tissues were excised and the RNA was isolated and analyzed for proinflammatory mediators [interleukin-1, (IL-1,), tumor necrosis factor-, (TNF-,), IL-6], T helper type 1 and type 2 cytokines [interferon-, (IFN-,), IL-4, IL-10), antioxidant enzymes [catalase (CAT), superoxide dismutase (SOD)], and genes critical for eicosanoid mediator production [cyclo-oxygenase-2 (COX-2), 5-lipoxygenase (5-LO)] by reverse transcription-polymerase chain reaction using rat-specific primers. Results:, Rats on the ,-3 FA diet exhibited decreased proinflammatory cytokine gene expression (IL-1,, TNF-,) and enhanced IFN-,, CAT and SOD messenger RNA expression compared to rats fed a corn oil diet, supporting a diet-induced modulation of host inflammatory reactions. Analyses of alveolar bone resorption in the rats related to gene expression profiles demonstrated significant positive correlations with IL-1,, IL-6 and COX-2 and negative correlations with CAT and SOD. Conclusion:, These findings suggest that diets enriched for ,-3 FA modulate the local gingival inflammatory milieu of the host following oral P. gingivalis infection, which impacts on alveolar bone resorption in rats. [source]

    Rosiglitazone treatment attenuates renal tissue inflammation generated by urinary tract obstruction

    NEPHROLOGY, Issue 2 2009
    SHAI EFRATI
    SUMMARY Aim: Peroxisome proliferator-activated receptor (PPAR)-, activation by rosiglitazone decreases manifestation of intrarenal inflammatory hallmarks. Inflammation significantly aggravates renal injury following urinary tract obstruction. The effect of rosiglitazone on renal inflammation following unilateral ureteral obstruction was investigated. Methods: Ninety-six Srague,Dawley rats were subjected to unilateral ureteral ligation, or to sham operation. Half of each group received rosiglitazone, 5 mg/kg bodyweight per day. The animals were killed and their kidneys allocated following 1 h, 24 h or 2 weeks, for pathological examination or for intrarenal transforming growth factor (TGF)-,, interleukin (IL)-4, IL-6, IL-10 and nitric oxide (NO) assessment by specific enzyme-linked immunosorbent assays. Apoptosis rates, extracellular matrix deposition, PPAR-,, ,-smooth muscle actin (,-SMA) expression and macrophage infiltration were assessed by specific immunohistological stainings. Results: PPAR-, receptor expression was downregulated, and infiltration of macrophages decreased, in all rosiglitazone-treated kidneys. Rosiglitazone significantly decreased apoptosis, TGF-,, IL-6, ,-SMA expression and NO availability in obstructed kidneys. Synthesis of IL-10 was unaltered, while IL-4 augmented by Rosiglitazone. Rosiglitazone also affected NO and IL-4 production in sham-operated controls. Conclusion: (i) Rosiglitazone attenuates profibrotic and pro-inflammatory responses in a rat model of ureteral obstruction-induced renal inflammation; (ii) rosiglitazone stimulates counteractive anti-inflammatory responses in the damaged kidneys; (iii) in part, rosiglitazone exerts comparable anti-inflammatory effects on obstructed kidneys and unobstructed healthy controls. Taken together, this ascertains the importance of the anti-inflammatory role of rosiglitazone treatment in amelioration of ureteral obstruction-induced renal damage. [source]

    Primate models in women's health: inflammation and atherogenesis in female cynomolgus macaques (Macaca fascicularis)

    AMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009
    Thomas C. Register
    Abstract Female cynomolgus monkeys are excellent models for understanding cardiovascular disease and the relationships between inflammatory processes and conditions such as atherogenesis. This review summarizes published research findings obtained through comprehensive, multidisciplinary, multi-investigator studies in nonhuman primates over the past two decades. These studies examined the effects of exogenous estrogens and dietary soy protein/isoflavones (IFs) on atherosclerosis, circulating biomarkers, and tissue inflammation in pre- and postmenopausal female cynomolgus monkeys. Inflammation may play a role in the initiation and progression of disease, be a consequence of the disease, or both. Circulating and tissue biomarkers with inflammatory and anti-inflammatory characteristics (including adhesion molecules such as e-selectin, VCAM-1, and ICAM-1, chemokines such as MCP-1, cytokines such as interleukins, and acute phase reactants such as CRP, and others) may be useful indicators of disease status. Treatment of postmenopausal subjects with estrogen resulted in significant reductions in several key inflammatory mediators as well as atherosclerosis, while dietary IF had a more limited effect on inflammation and atherogenesis. Circulating concentrations of key inflammatory proteins, including monocyte-chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6), were associated with atherosclerosis and lesion characteristics in these animals. In premenopausal female monkeys, a diet enriched in soy protein reduced arterial inflammation as well as atherogenesis in comparison to a diet enriched in casein-lactalbumin. Expression levels of arterial inflammation associated genes (MCP-1, ICAM-1) and markers for inflammatory cell types (macrophages and T cells) correlated with plaque size, were differentially influenced by treatments, and represent potential targets for interventions. Arterial expression of estrogen receptor ,, the key mediator of estrogenic effects, was inversely correlated with plaque size and indices of inflammation, suggestive of an atheroprotective role. The findings provide additional evidence that circulating inflammatory markers (particularly MCP-1) may be useful indicators of atherosclerotic disease progression and responses to treatment in female primates, and that estrogens and dietary soy may inhibit atherogenesis in part through anti-inflammatory mechanisms. Am. J. Primatol. 71:766,775, 2009. © 2009 Wiley-Liss, Inc. [source]

    Alloimmune Activation Enhances Innate Tissue Inflammation/Injury in a Mouse Model of Liver Ischemia/Reperfusion Injury

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010
    X. Shen
    The deleterious sensitization to donor MHC Ags represents one of the most challenging problems in clinical organ transplantation. Although the role of effector/memory T cells in the rejection cascade has been extensively studied, it remains unknown whether and how these ,Ag-specific' cells influence host innate immunity, such as tissue inflammation associated with ischemia and reperfusion injury (IRI). In this study, we analyzed how allogeneic skin transplant (Tx) affected the sequel of host's own liver damage induced by partial warm ischemia and reperfusion. Our data clearly showed that allo-Tx recipients had increased inflammatory response against IR insult in their native livers, as evidenced by significantly more severe hepatocelluar damage, compared with syngeneic Tx recipient controls, and determined by serum ALT levels, liver histology (Suzuki's score) and intrahepatic proinflammatory gene inductions (TNF-,, IL-1, and CXCL10). The CD4 T cells, but neither CD8 nor NK cells, mediated the detrimental effect of allo-Ag sensitization in liver IRI. Furthermore, CD154, but not IFN-,, was the key mechanism in allo-Tx recipients to facilitate IR-triggered liver damage. These results provide new evidence that alloreactive CD4 T cells are capable of enhancing innate tissue inflammation and organ injury via an Ag-nonspecific CD154-dependent but IFN-, independent mechanism. [source]

    Specific central nervous system recruitment of HLA-G+ regulatory T cells in multiple sclerosis,

    ANNALS OF NEUROLOGY, Issue 2 2009
    Yu-Hwa Huang MSci
    Objective We have recently described a novel population of natural regulatory T cells (Treg) that are characterized by the expression of HLA-G and may be found at sites of tissue inflammation (HLA-Gpos Treg). Here we studied the role of these cells in multiple sclerosis (MS), a prototypic autoimmune inflammatory disorder of the central nervous system (CNS). Methods Sixty-four patients with different types of MS, 9 patients with other neurological diseases, and 20 healthy donors were included in this study. Inflamed brain lesions from 5 additional untreated MS patients were examined. HLA-Gpos Treg were analyzed in the cerebrospinal fluid (CSF) by flow cytometry and in inflammatory demyelinating lesions of MS brain specimens by immunohistochemistry. Functional capacity was accessed and transmigration was determined using an in vitro model of the human blood-brain barrier (BBB). Results HLA-Gpos Treg were found enriched in the inflamed CSF of MS patients and in inflammatory demyelinating lesions of MS brain specimens. HLA-Gpos Treg showed a strong propensity to transmigrate across BBB, which was vigorously driven by inflammatory chemokines, and associated with a gain of suppressive capacity upon transmigration. CSF-derived HLA-Gpos Treg of MS patients represented a population of activated central memory activated T cells with an upregulated expression of inflammatory chemokine receptors and exhibiting full suppressive capacity. Unlike natural FoxP3-expressing Treg, HLA-Gpos Treg derived from peripheral blood were functionally unimpaired in MS. Interpretation In MS, HLA-Gpos Treg may serve to control potentially destructive immune responses directly at the sites of CNS inflammation and to counterbalance inflammation once specifically recruited to the CNS. Ann Neurol 2009 [source]

    Promotion of the local differentiation of murine Th17 cells by synovial macrophages during acute inflammatory arthritis

    ARTHRITIS & RHEUMATISM, Issue 12 2008
    Paul J. Egan
    Objective To examine the generation of proinflammatory Th17 cells at the site of tissue inflammation and in draining lymph nodes using an interleukin-17 (IL-17),dependent model of acute inflammatory arthritis. Methods Arthritis was elicited in mice by intraarticular injection of methylated bovine serum albumin (mBSA) into the knee and subcutaneous injection of IL-1,. Anti,IL-17 or control antibodies were administered during arthritis induction. Cytokine expression was evaluated by intracellular cytokine staining of synovial lymphocytes, by polymerase chain reaction analysis of RNA extracted from lymph node cells, and by enzyme-linked immunosorbent assay of cell culture supernatants. Th17 differentiation of naive CD4+ T cells was assessed in cocultures with macrophages from arthritic mice. Results Anti,IL-17 antibody administered during acute arthritis markedly reduced disease, indicating that the model is IL-17 dependent. IL-17 messenger RNA (mRNA), but not protein, was detected in draining lymph node CD4+ T cells and preceded joint inflammation. In addition, mRNA for Th17 cell,stimulatory cytokines (transforming growth factor ,, IL-6) and Th17 cell,inhibitory cytokines (interferon-,, IL-4) was detected in lymph nodes following injection of mBSA and IL-1,. Th17 cells were clearly identified in the inflamed synovium at the peak of disease. Synovial macrophages supported Th17 cell generation from naive CD4+ T cell precursors stimulated via CD3 in vitro and produced high levels of IL-6. In contrast, peritoneal macrophages failed to induce Th17 cell differentiation and produced less IL-6. Conclusion These results suggest that Th17 cell differentiation is initiated in draining lymph nodes but that IL-17,producing cells are restricted to the inflamed synovium, being generated in response to local cytokines produced by inflammatory macrophages. [source]

    Chronic arthritis aggravates vascular lesions in rabbits with atherosclerosis: A novel model of atherosclerosis associated with chronic inflammation

    ARTHRITIS & RHEUMATISM, Issue 9 2008
    Raquel Largo
    Objective To determine whether systemic inflammation induced by chronic antigen-induced arthritis (AIA) accelerates vascular lesions in rabbits with atherosclerosis. Methods Two models of atherosclerosis and chronic AIA were combined. Atherosclerosis was induced by coupling a hyperlipemic diet with an endothelial lesion at the femoral arteries, while chronic AIA was induced by ovalbumin injection. Markers in sera and peripheral blood mononuclear cells (PBMCs) as well as vessels and synovial membranes from the rabbits with the double phenotype (both chronic AIA and atherosclerosis) were compared with those from rabbits with each disease alone. Results Serum levels of interleukin-6, C-reactive protein, and prostaglandin E2 increased in rabbits with both chronic AIA and atherosclerosis as compared with healthy animals or animals with either chronic AIA alone or atherosclerosis alone. NF-,B binding and CCL2 and cyclooxygenase 2 (COX-2) expression were higher in PBMCs from rabbits with both chronic AIA and atherosclerosis than in PBMCs from healthy rabbits. The intima-media thickness ratio of femoral arteries was equally increased in rabbits with atherosclerosis alone and in rabbits with both chronic AIA and atherosclerosis, but the latter group showed a higher level of macrophage infiltration. Femoral CCL2 and COX-2 expression was increased in rabbits with both chronic AIA and atherosclerosis as compared with rabbits with atherosclerosis alone. In the aortas, vascular lesions were found in 27% of rabbits with atherosclerosis alone and in 60% of rabbits with both chronic AIA and atherosclerosis. Rabbits with both chronic AIA and atherosclerosis exhibited more severe synovitis and higher synovial expression of CCL2 than did rabbits with chronic AIA alone. Conclusion The onset of chronic AIA in animals with atherosclerosis resulted in the local and systemic up-regulation of mediators of tissue inflammation and plaque instability associated with a higher incidence of aortic lesions. This model could represent a novel approach to the study of inflammation-associated atherosclerosis. [source]

    In vivo effects of CB2 receptor-selective cannabinoids on the vasculature of normal and arthritic rat knee joints

    BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008
    J J McDougall
    Background and purpose: Cannabinoids (CBs) are known to be vasoactive and to regulate tissue inflammation. The present study examined the in vivo vasomotor effects of the CB2 receptor agonists JWH015 and JWH133 in rat knee joints. The effect of acute and chronic joint inflammation on CB2 receptor-mediated responses was also tested. Experimental approach: Blood flow was assessed in rat knee joints by laser Doppler imaging both before and following topical administration of CB2 receptor agonists. Vasoactivity was measured in normal, acute kaolin/carrageenan inflamed and Freund's complete adjuvant chronically inflamed knees. Key results: In normal animals, JWH015 and JWH133 caused a concentration-dependent increase in synovial blood flow which in the case of JWH133 was blocked by the selective CB2 receptor antagonist AM630 as well as the transient receptor potential vanilloid-1 (TRPV1) antagonist SB366791. The vasodilator effect of JWH133 was significantly attenuated in both acute and chronically inflamed knees. Given alone, AM630 had no effect on joint blood flow. Conclusion and implications: In normal joints, the cannabinomimetic JWH133 causes hyperaemia via a CB2 and TRPV1 receptor mechanism. During acute and chronic inflammation, however, this vasodilatatory response is significantly attenuated. British Journal of Pharmacology (2008) 153, 358,366; doi:10.1038/sj.bjp.0707565; published online 5 November 2007 [source]

    Role of interleukin-17F in chronic inflammatory and allergic lung disease

    CLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2006
    N. Hizawa
    Summary IL-17 family members belong to a distinct category of cytokines that coordinate local tissue inflammation by inducing the release of pro-inflammatory and neutrophil-mobilizing cytokines. The importance of the IL-17 family in inflammatory and autoimmune disease is becoming increasingly apparent. IL-17F is a recently discovered member of the IL-17 family that has a number of biological activities through induction of various cytokines, chemokines, and mediators. IL-17A, the founding member of the IL-17 family, and IL-17F are produced by several inflammatory cells, including activated T cells, in response to infectious and antigenic stimuli. Overexpression of IL-17A or IL-17F in the lungs results in induction of CXC chemokines and neutrophil recruitment. In a case,control study of 1125 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL17F gene was shown to be associated with asthma and chronic obstructive pulmonary disease (COPD). Functionally, this variant failed to induce cytokines and chemokines, and interestingly, was able to antagonize the activity of wild-type IL-17F. These results provide an experimental basis for the observed genetic association with chronic inflammatory lung diseases, and also suggest the potential therapeutic utility of this antagonistic variant of IL-17F. Given that asthma and COPD are complex diseases involving a number of genetic and environmental factors, the genetic impact of IL-17F H161R with regard to the development of chronic airway inflammation likely varies among individuals with different genetic backgrounds and environmental exposures. [source]

    Resuscitation with Na+/H+ exchanger inhibitor in traumatic haemorrhagic shock: Cardiopulmonary performance, oxygen transport and tissue inflammation

    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2010
    Dongmei Wu
    Summary 1. The aim of the present study was to examine the effects of inhibition of the Na+/H+ exchanger (NHE-1) on cardiopulmonary performance, oxygen carrying capacity and tissue inflammation in a pig model of traumatic haemorrhage,resuscitation. 2. In 12 instrumented anaesthetized pigs, traumatic haemorrhage was modelled by producing tibia fractures, followed by haemorrhage of 25 mL/kg for 20 min, and then a 4 mm hepatic arterial tear with surgical repair after 20 min. Animals then underwent low-volume fluid resuscitation with either Hextend (vehicle; n = 6; Hospira, Lake Forest, IL, USA) or 3 mg/kg BIIB513 (an NHE-1 inhibitor) + Hextend (n = 6). The experiment was terminated 6 h after the beginning of resuscitation. 3. Compared with vehicle-treated controls, the addition of NHE-1 inhibition with BIIB513 significantly improved the left ventricle stroke work index and attenuated increases in pulmonary arterial pressure and pulmonary vascular resistance. Furthermore, BIIB513 treatment significantly increased the oxygenated haemoglobin ratio, blood oxygen content and mixed venous blood oxygen saturation and improved blood oxygen delivery. In addition, BIIB513 treatment reduced lung tissue levels of interleukin-6 by 80%, tumour necrosis factor-, by 37% and myeloperoxidase activity by 38%. Nuclear factor-,B DNA binding activity in the lung was also slightly and significantly attenuated following BIIB513 treatment. 4. In conclusion, the present study shows that NHE-1 inhibition facilitates the response to fluid resuscitation after traumatic haemorrhage by improving cardiac function, pulmonary vascular function and oxygen carrying capacity, which results in reduced tissue inflammatory injury. [source]

    Minimally Invasive Flapless Implant Surgery: A Prospective Multicenter Study

    CLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH, Issue 2005
    ODhc, William Becker DDS
    ABSTRACT Background: Placement of implants with a minimally invasive flapless approach has the potential to minimize crestal bone loss, soft tissue inflammation, and probing depth adjacent to implants and to minimize surgical time. Purpose: The aim of this multicenter study was to evaluate implant placement using a minimally invasive one-stage flapless technique up to 2 years. Materials and Methods: Fifty-seven patients ranging in age from 24 to 86 years were recruited from three clinical centers (Tucson, AZ, USA; Tel Aviv, Israel; Göteborg, Sweden). Seventy-nine implants were placed. A small, sharp-tipped guiding drill was used to create a precise, minimally invasive initial penetration through the mucosa and into bone (Nobel Biocare, Yorba, Linda, CA, USA). Implants were placed according to the manufacturer's instructions, with minimal countersinking. The parameters evaluated were total surgical time, implant survival, bone quality and quantity, implant position by tooth type, depth from mucosal margin to bone crest, implant length, probing depth, inflammation, and crestal bone changes. At 2 years, for 79 implants placed in 57 patients, the cumulative success rate using a minimally invasive flapless method was 98.7%, indicating the loss of 1 implant. Changes in crestal bone for 77 baseline and follow-up measurements were insignificant (radiograph 1: mean 0.7 mm, SD 0.5 mm, range 2.8 mm, minimum 0.2 mm, maximum 3.0 mm; radiograph 2: mean 0.8 mm, SD 0.5 mm, range 3.4 mm, minimum 0.12 mm, maximum 3.5 mm). Using descriptive statistics for 78 patients (one implant lost), mean changes for probing depth and inflammation were clinically insignificant. The average time for implant placement was 28 minutes (minimum 10 minutes, maximum 60 minutes, SD 13.1 minutes). Average depth from mucosal margin to bone was 3.3 mm (SD 0.7 mm, minimum 2 mm, maximum 5 mm, range 3 mm). Thirty-two implants were placed in maxillae and 47 in mandibles. Conclusions: The results of this study demonstrate that following diagnostic treatment planning criteria, flapless surgery using a minimally invasive technique is a predictable procedure. The benefits of this procedure are lessened surgical time; minimal changes in crestal bone levels, probing depth, and inflammation; perceived minimized bleeding; and lessened postoperative discomfort. [source]

    Fixed Implant-Supported Prostheses in Elderly Patients: A 5-Year Retrospective Study of 133 Edentulous Patients Older than 79 Years

    CLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH, Issue 4 2004
    Ingela Engfors DDS
    ABSTRACT Background: An increasing number of elderly patients are treated with implants, but results for the elderly patient in terms of implant success and adaptation to implant prostheses are contradictory. Objective: To retrospectively study the 5-year clinical and radiologic performances of fixed implant-supported prostheses placed in edentulous elderly patients and to compare those results with the results of using similar prostheses in a control group of younger patients. Materials and Methods: The study group comprised 133 edentulous patients who were 80 or more years of age and who were consecutively treated with fixed implant-supported prostheses between January 1986 and August 1998. Altogether 761 Brånemark System® implants (Nobel Biocare AB, Göteborg, Sweden) were placed in 139 edentulous jaws. The control group comprised 115 edentulous patients who were younger than 80 years and who were treated consecutively from March 1996 to November 1997 with similar prostheses. In this group 670 implants were placed in 118 edentulous jaws. Information was collected from all postinsertion visits, including the fifth annual checkup, and changes of marginal bone levels were analyzed from intraoral radiographs. Results: The 5-year cumulative survival rate (CSR) for implants in the maxilla was 93.0% in the study group and 92.6% in the control group; the corresponding CSRs for implants in the mandible were 99.5% and 99.7%. The most common complications for patients in the study group were soft tissue inflammation (mucositis) and cheek and lip biting (p < .05) whereas resin veneer fractures were the most common complications for the control group. Overall 5-year marginal bone loss for the study group was 0.7 mm (standard deviation [SD], 0.45) in the upper jaw and 0.6 mm (SD, 0.50) in the lower jaw. Differences in bone levels and bone loss between the two groups did not reach significant levels (p > .05). Conclusions: Implant treatment in the elderly patients showed treatment results comparable to those observed in younger age groups. However, indications of more problems with adaptation could be observed and were reflected in more postinsertion problems. Cleaning problems and associated soft tissue inflammation (mucositis) as well as tongue, lip, and cheek biting were significantly more often observed among the elderly patients (p < .05). [source]

    Reconstruction of maxillary and mandibular defects using prefabricated microvascular fibular grafts and osseointegrated dental implants , a prospective study

    CLINICAL ORAL IMPLANTS RESEARCH, Issue 5 2004
    Claude Jaquiéry
    Abstract: The fibular flap can be used for a variety of indications. Recently, the treatment of four patients with severely atrophied upper jaws using a method to prefabricate the vascularized fibular graft has been published. This technique consists of a two-stage operation procedure that allows simultaneous prosthodontic rehabilitation and immediate placement of dental implants. In this paper eight patients with 29 ITI implants (Straumann AG, Waldenburg, Switzerland) who had reconstruction of either the upper or lower jaw are presented. The aim of the study was (i) to evaluate the behavior of the newly formed soft tissue around implants inserted in the fibula by applying periodontal parameters, (ii) to monitor prospectively the integration of the implants in the fibular graft, and (iii) to assess the osseous integration of the fibular graft used for reconstruction of the upper or lower jaw. Two implants failed during the observation time because of avascular bone at the distal end of the fibular graft. Stabilization of the graft, however, was never compromised. Due to the prefabrication firmly attached gingiva-like soft tissue could be provided preventing periimplant soft tissue inflammation and facilitating oral hygiene. After 1 year of observation the mean attachment level was similar to implants placed in original bone whereas vertical bone loss measured radiographically was lower in the present study. This may indicate that the remodeling of a bicortical bone requires a longer period of time compared with the bone of the alveolar crest. The prospective 1-year results are promising but long-term evaluation of periodontal and radiological parameters are required. Résumé Le lambeau péroné peut être utilisé pour une variété d'indications. Récemment le traitement de quatre patients avec une atrophie sévère des mâchoires supérieures et utilisant une méthode pour préfabriquer un greffon péroné vascularisé a été publié. Cette technique consiste en une opération en deux étapes qui permet la réhabilitation prothétique simultanée et le placement immédiat des implants dentaires. Dans ce rapport huit patients avec 29 implants ITI (Straumann AG, Waldenburg, Switzerland) ont eu une reconstruction de la mâchoire supérieure ou inférieure. Le but de cette étude a été 1) d'évaluer le comportement des tissus mous nouvellement formés autour des implants insérés dans le péroné en appliquant les paramètres parodontaux, 2) de suivre d'une manière prospective l'intégration des implants dans le greffon péroné et 3) d'examiner l'intégration osseuse de l'implant péroné utilisé pour la reconstruction de ces mâchoires. Deux implants ont échoué durant la période d'observation parce que l'os alvéolaire n'était pas vasculariséà la partie distale du greffon. La stabilisation du greffon n'a cependant jamais été compromise. La préfabrication d'un tissu ressemblant à de la gencive préfabriquée a permit d'éviter l'inflammation gingivale et de faciliter l'hygiène buccale. Après une année d'observation le niveau d'attache moyen était semblable au niveau des implants placés dans l'os original tandis que la perte osseuse verticale mesurée radiographiquement était inférieure dans l'étude présente. Ceci peut indiquer que le remodelage de l'os bicortical requiert une période plus importante comparée à l'os du rebord alvéolaire. Ces résultats prospectifs à une année sont encourageants mais l'évaluation à long terme des paramètres parodontaux et radiologiques reste encore nécessaire. Zusammenfassung Der Fibula-Lappen kann bei einer Vielzahl von Indikationen angewendet werden. Kürzlich wurde eine Publikation über die Behandlung von vier Patienten mit stark atrophierten Oberkiefern mittels vorfabrizierten vaskularisierten Fibula transplantaten veröffentlicht. Diese Technik besteht aus einer Operation in zwei Phasen, welche die Sofortimplantation von dentalen Implantaten und gleichzeitige prothetische Rekonstruction erlaubt. In diesem Artikel werden acht Patienten mit 29 Implantaten (Straumann AG, Waldenburg, Switzerland), bei welchen entweder eine OK- oder UK-Rekonstruktion durchgeführt wurde, präsentiert. Das Ziel der Studie war (i) das Verhalten des neu gebildeten Gewebes um die Implantate, welche in die Fibula eingesetzt worden waren mittels parodontalen Parametern zu untersuchen, (ii) die Integration der Implantate in das Fibula-Transplantat prospektiv aufzuzeichnen und (iii) die ossäre Integration des für die Rekonstruktion des OK oder UK verwendeten Fibula-Transplantats zu ermitteln. Zwei Implantate zeigten während der Beobachtungsperiode Misserfolge wegen avaskulärem Knochen an den distalen Enden des Fibula-Transplantats. Die Stabilisierung des Transplantats war jedoch niemals beeinträchtigt. Durch die Vorfabrizierung konnten gut angewachsene gingiva-ähnliche Weichgewebe geschaffen werden, welche eine periimplantäre Entzündung der Weichgewebe verhinderten und die Mundhygiene erleichterten. Nach einer Beobachtungszeit von einem Jahr war das mittlere Attachmentniveau ähnlich dem von Implantaten, welche in alveolären Knochen inseriert worden waren, während der radiologisch gemessene Knochenverlust in der vorliegenden Studie geringer war. Dies könnte ein Indiz dafür sein, dass die Remodellierung eines bikortikalen Knochens im Vergleich zum Alveolarknochen längere Zeit benötigt. Die prospektiven Resultate nach einem Jahr sehen vielversprechend aus, aber es muss eine Auswertung der parodontalen und radiologischen Parameter über einen längeren Zeitraum durchgeführt werden. Resumen El colgajo peroneal puede ser usado para una variedad de indicaciones. Recientemente se ha publicado el tratamiento de cuatro pacientes con maxilares superiores severamente atróficos usando un método para prefabricar el injerto peroneal vascularizado. Esta técnica consiste en un procedimiento de operación de dos fases que permite la rehabilitación prostodóntica y la colocación inmediata de implantes dentales simultáneamente. En este artículo se presentan ocho pacientes con 29 implantes ITI (Strauman AG, Waldenburg) teniendo una reconstrucción de tanto el maxilar superior como del inferior. La intención del presente estudio fue (i) evaluar el comportamiento de del tejido blando neoformado alrededor de los implantes insertados en la tibia aplicando parámetros periodontales, (ii) monitorizar prospectivamente la integración de los implantes en el injerto perineal y (iii) valorar la integración ósea del injerto perineal usado para la reconstrucción del maxilar superior o inferior. Dos implantes fracasaron durante el periodo de observación debido a hueso sin vascularización en el final distal del injerto perineal. De todos modos, la estabilización del injerto no se vio nunca comprometida. Debido a la prefabricación se pudo suministrar un tejido blando tipo encía adherida previniendo inflamación del tejido blando periimplantario y facilitando la higiene oral. Tras un año de observación el nivel de inserción medio fue similar a los implantes insertados en las áreas de hueso original mientras que la pérdida de hueso vertical medida radiograficamente fue menor en el presente estudio. Esto puede indicar que el remodelado de un hueso bicortical requiere un periodo mas largo de tiempo comparado con el hueso de la cresta alveolar. Los resultados prospectivos de un año son prometedores pero se requieren evaluaciones de los parámetros periodontales y radiológicos a largo plazo. [source]