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Various Inflammatory Conditions (various + inflammatory_condition)
Selected AbstractsKnocking out IL-6 by vaccinationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2004Pia Galle Abstract Inappropriate expression of IL-6 plays a role in various inflammatory conditions, degenerative diseases, and cancers. Several model systems have been developed that can specifically block IL-6-receptor interactions. Here we present a simple and highly effective approach based on vaccination with a pool of specifically mutated IL-6 analogues to induce a neutralizing IL-6 antibody responsein mice. Judged by the ability of the analogues to bind to heterologous anti-IL-6 antibodies and cellular IL-6 receptors the IL-6 analogues seemed to have a three-dimensional structure comparable to that of wild-type IL-6. Injection of them broke self-tolerance and induced an immune response to IL-6, presumably because of the amino acid differences between the analogues and wild-type IL-6. This resulted in a long-lasting anti-IL-6 antibody-mediated IL-6 deficiency that blocked experimentally induced IL-6-mediated pathology. [source] Mice with neonatally induced inactivation of the vascular cell adhesion molecule-1 fail to control the parasite in Toxoplasma encephalitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2003Martina Deckert Abstract Under various inflammatory conditions, cell adhesion molecules are up-regulated in the central nervous system (CNS) and may contribute to the recruitment of leukocytes to the brain. In the present study, the functional role of vascular cell adhesion molecule (VCAM)-1 in Toxoplasma encephalitis (TE) was addressed using VCAMflox/flox MxCre mice. Neonatal inactivation of the VCAM-1 gene resulted in a lack of induction of VCAM-1 on cerebral blood vessel endothelial cells, whereas the constitutive expression of VCAM-1 on choroid plexus epithelial cells and the ependymawas unaffected; in these animals, resistance to T.,gondii was abolished, and VCAMflox/flox MxCre mice died of chronic TE caused by a failure to control parasites in the CNS. Although leukocyte recruitment to the CNS was unimpaired, the B cell response was significantly reduced as evidenced by reduced serum levels of anti- T.,gondii -specific IgM and IgG antibodies. Furthermore, the frequency and activation state of intracerebral T.,gondii -specific T cells were decreased, and microglial activation was markedly reduced. Taken together, these data demonstrate the crucial requirement of VCAM-1-mediated immune reactions for the control of an intracerebral infectious pathogen, whereas other cell adhesion molecules can efficiently compensate for VCAM-1-mediated homing across cerebral blood vessels. [source] Serum YKL-40 as a marker of disease activity and stricture formation in patients with Crohn's diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8pt2 2008Yusuf Erzin Abstract Background and Aim:, YKL-40 is secreted by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated serum levels of YKL-40 have been reported in patients with various inflammatory conditions and ongoing fibrosis. The aim of this study was to investigate the relationship between serum concentrations of YKL-40 and disease activity, acute phase reactants, and the presence of strictures in patients with Crohn's disease (CD). Methods:, We studied the serum concentrations of YKL-40 in 41 patients with CD, in which 12 had an endoscopically- or radiologically-proven stricture formation. Forty-six age- and sex-matched healthy volunteers served as controls and a multivariate regression analysis was performed to find out the independent predictors of intestinal strictures and clinical activity. Results:, The serum YKL-40 concentrations in the patients were significantly higher than that in the healthy controls (105.69 ± 88.08 ng/mL [range 20.23,333.57]vs 44.92 ± 24.89 ng/mL [range 18.31,113.43], P = 0.000) and patients with a stricture formation had significantly higher YKL-40 levels than those without strictures (167.50 ± 119.30 ng/mL [range 23.62,333.57]vs 80.12 ± 56.38 ng/mL [range 20.23,259.19], P = 0.003). Significant correlations were noted between YKL-40 levels and clinical activity (r = 0.681; P = 0.000) and the presence of intestinal strictures (r = 0.457; P = 0.003). The multivariate regression analysis found the serum YKL-40 levels to be an independent predictor of intestinal strictures (P = 0.001) and clinical activity (P = 0.001). Conclusion:, Patients with CD, particularly those with a stricture formation, have significantly higher levels of YKL-40. YKL-40 seems to be a useful marker of disease activity as well as stricture formation in patients with CD. [source] Melatonin inhibits lipopolysaccharide-induced CC chemokine subfamily gene expression in human peripheral blood mononuclear cells in a microarray analysisJOURNAL OF PINEAL RESEARCH, Issue 2 2007Hae Jeong Park Abstract:, Melatonin possesses a number of important biologic activities including oncostatic, anti-oxidant, and immunostimulatory actions. This study was designed to assess the effects of melatonin on inflammation-related gene expression in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs), using CombiMatrix 2K Human Inflammation chip. After pretreatment with melatonin (100 ,m) for 4 hr, cells were incubated with LPS (1 ,g/mL) for 24 hr. We compared gene expression profiles between LPS-treated, melatonin-treated, LSP/melatonin-treated, and control groups. LPS induced the upregulation of 95 genes, compared with controls. Melatonin pretreatment in LPS-stimulated PBMCs suppressed the expression of 23 genes more than twofold. Interestingly, melatonin showed a suppressive effect on the expression of CC chemokine subfamily genes, including CCL2/MCP1, CCL3/MIP1,, CCL4/MIP1,, CCL5/RANTES, CCL8/MCP2, CCL20/MDC, and CCL22/MIP3,, in LPS-stimulated PBMCs. This result was confirmed by reverse transcriptase polymerase chain reaction. Among the CC chemokine subfamily genes, particularly, the expression of CCL2 and CCL5 was markedly downregulated by melatonin in LPS-stimulated PBMCs. The secretion levels of CCL2 and CCL5 were measured using enzyme-linked immunosorbent assay. Stimulation of PBMCs by LPS induced the secretion of CCL2 (2334.3 ± 161.4 pg/mL, mean ± S.E.M.), whereas melatonin pretreatment (153.0 ± 3.8 pg/mL) inhibited the LPS-induced secretion of CCL2. Melatonin pretreatment (2696.2 ± 385.3 pg/mL) also inhibited the LPS-induced secretion of CCL5 (4679.6 ± 107.5 pg/mL). Taken together, these results suggest that melatonin may have a suppressive effect on LPS-induced expression of CC chemokine genes, especially CCL2 and CCL5, which may explain its beneficial effects in the treatment of various inflammatory conditions. [source] Liver distribution of ,,-T-cells in patients with chronic hepatitis of different etiologyAPMIS, Issue 11 2009HANS-UDO KASPER The ,, T cells represent a minor unique T-cell subpopulation long been considered as innate-like immune cells. They are found in increased numbers in tissues from various inflammatory conditions. Their role in chronic hepatitis, however, is still discussed controversially. Fresh frozen tissues from 50 patients (18 cases hepatitis B infection, 25 hepatitis C, three cases with co-infection of hepatitis B and C and four patients with autoimmune hepatitis) were investigated. Immunohistochemistry with primary antibodies detecting ,, and ,, TCR was used to evaluate their incidence and distribution in the different histological structures of the liver. The inflammatory infiltrate in all cases of chronic hepatitis was dominated by ,, T cells and was mainly localized in the portal tracts with formation of an interface hepatitis (95.3%,, T cells; 4.7%,, T cells). There were neither significant differences between inflammatory infiltrate nor the amount or percentage of ,, T cells between hepatitis B, C or autoimmune hepatitis. No accumulation of ,, T cells could be observed in cases of chronic hepatitis of different etiologies. The immune-mediated phenomena in chronic hepatitis are dominated by ,, T cells. Thus, the adapted immune system is responsible for the inflammatory processes in chronic hepatitis. [source] Prostanoid receptor antagonists: development strategies and therapeutic applicationsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2009RL Jones Identification of the primary products of cyclo-oxygenase (COX)/prostaglandin synthase(s), which occurred between 1958 and 1976, was followed by a classification system for prostanoid receptors (DP, EP1, EP2 ,) based mainly on the pharmacological actions of natural and synthetic agonists and a few antagonists. The design of potent selective antagonists was rapid for certain prostanoid receptors (EP1, TP), slow for others (FP, IP) and has yet to be achieved in certain cases (EP2). While some antagonists are structurally related to the natural agonist, most recent compounds are ,non-prostanoid' (often acyl-sulphonamides) and have emerged from high-throughput screening of compound libraries, made possible by the development of (functional) assays involving single recombinant prostanoid receptors. Selective antagonists have been crucial to defining the roles of PGD2 (acting on DP1 and DP2 receptors) and PGE2 (on EP1 and EP4 receptors) in various inflammatory conditions; there are clear opportunities for therapeutic intervention. The vast endeavour on TP (thromboxane) antagonists is considered in relation to their limited pharmaceutical success in the cardiovascular area. Correspondingly, the clinical utility of IP (prostacyclin) antagonists is assessed in relation to the cloud hanging over the long-term safety of selective COX-2 inhibitors. Aspirin apart, COX inhibitors broadly suppress all prostanoid pathways, while high selectivity has been a major goal in receptor antagonist development; more targeted therapy may require an intermediate position with defined antagonist selectivity profiles. This review is intended to provide overviews of each antagonist class (including prostamide antagonists), covering major development strategies and current and potential clinical usage. [source] Volatile organic compounds in exhaled breath as a diagnostic tool for asthma in childrenCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2010J. W. Dallinga Summary Background The correct diagnosis of asthma in young children is often hard to achieve, resulting in undertreatment of asthmatic children and overtreatment in transient wheezers. Objectives To develop a new diagnostic tool that better discriminates between asthma and transient wheezing and that leads to a more accurate diagnosis and hence less undertreatment and overtreatment. A first stage in the development of such a tool is the ability to discriminate between asthmatic children and healthy controls. The integrative analysis of large numbers of volatile organic compounds (VOC) in exhaled breath has the potential to discriminate between various inflammatory conditions of the respiratory tract. Methods Breath samples were obtained and analysed for VOC by gas chromatography,mass spectrometry from asthmatic children (n=63) and healthy controls (n=57). A total of 945 determined compounds were subjected to discriminant analysis to find those that could discriminate diseased from healthy children. A set of samples from both asthmatic and healthy children was selected to construct a model that was subsequently used to predict the asthma or the healthy status of a test group. In this way, the predictive value of the model could be tested. Measurements and main results The discriminant analyses demonstrated that asthma and healthy groups are distinct from one another. A total of eight components discriminated between asthmatic and healthy children with a 92% correct classification, achieving a sensitivity of 89% and a specificity of 95%. Conclusion The results show that a limited number of VOC in exhaled air can well be used to distinguish children with asthma from healthy children. Cite this as: J. W. Dallinga, C. M. H. H. T. Robroeks, J. J. B. N. van Berkel, E. J. C. Moonen, R. W. L. Godschalk, Q. Jöbsis, E. Dompeling, E. F. M. Wouters and F. J. van Schooten, Clinical & Experimental Allergy, 2010 (40) 68,76. [source] | ||||||||||