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Chemokine Levels (chemokine + level)
Kinds of Chemokine Levels Selected AbstractsSmoke Exposure and Ethanol Ingestion Modulate Intrapulmonary Polymorphonuclear Leukocyte Killing, but Not Recruitment or PhagocytosisALCOHOLISM, Issue 9 2006Elizabeth A. Vander Top Background: People who smoke and abuse alcohol are uniquely susceptible to pulmonary infections caused by Streptococcus pneumoniae, the pneumococcus. The primary cellular defense against pneumococci within the lungs is the polymorphonuclear leukocyte (PMN). Cigarette smoke and ethanol (EtOH) are known to alter certain PMN functions, but little is known about their concurrent effects. Methods: Male Sprague,Dawley rats were exposed twice daily for 8 weeks to cigarette smoke (smoke-exposed) or room air (sham-exposed). During the final week of exposure, the rats were pair-fed a liquid diet containing either 36 or 0% EtOH calories. Polymorphonuclear leukocytes were prerecruited into the rats' lungs by transtracheal injection of lipopolysaccharide. Five hours later, the rats were infected transtracheally with S. pneumoniae, and PMN recruitment, phagocytosis, and bactericidal activity were quantified within their lungs. Chemokine levels were also measured in bronchoalveolar lavage fluids, lung homogenates, and sera. Results: Neither PMN recruitment nor phagocytic uptake of pneumococci was altered by EtOH ingestion or smoke exposure. Killing of the organisms, however, was significantly decreased in sham-exposed, but not smoke-exposed, rats ingesting EtOH. Parallel results were determined for serum cytokine-induced neutrophil chemoattractant-1 (CINC-1), with EtOH ingestion significantly decreasing the levels in sham-exposed, but not smoke-exposed, rats. Pulmonary levels of macrophage inflammatory protein-2 (MIP-2) and CINC-1 were highly elevated by the combination of EtOH and smoke. Conclusions: One week of EtOH ingestion by rats impaired the ability of their PMNs to kill S. pneumoniae within their lungs. This was not due to decreased recruitment of the PMNs to the lungs or to diminished phagocytosis of intrapulmonary pneumococci. The addition of twice-daily cigarette smoke exposure to this short-term EtOH ingestion model restored PMN bactericidal ability to levels observed in the absence of either treatment. These EtOH-induced and smoke-induced alterations in PMN killing may be related to alterations in both pulmonary and systemic inflammatory chemokine levels. [source] Interferon-regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: A validation studyARTHRITIS & RHEUMATISM, Issue 10 2009Jason W. Bauer Objective Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by unpredictable flares of disease activity and irreversible damage to multiple organ systems. An earlier study showed that SLE patients carrying an interferon (IFN) gene expression signature in blood have elevated serum levels of IFN-regulated chemokines. These chemokines were associated with more-severe and active disease and showed promise as SLE disease activity biomarkers. This study was designed to validate IFN-regulated chemokines as biomarkers of SLE disease activity in 267 SLE patients followed up longitudinally. Methods To validate the potential utility of serum chemokine levels as biomarkers of disease activity, we measured serum levels of CXCL10 (IFN,-inducible 10-kd protein), CCL2 (monocyte chemotactic protein 1), and CCL19 (macrophage inflammatory protein 3,) in an independent cohort of 267 SLE patients followed up longitudinally over 1 year (1,166 total clinic visits). Results Serum chemokine levels correlated with lupus activity at the current visit (P = 2 × 10,10), rising at the time of SLE flare (P = 2 × 10,3) and decreasing as disease remitted (P = 1 × 10,3); they also performed better than the currently available laboratory tests. Chemokine levels measured at a single baseline visit in patients with a Systemic Lupus Erythematosus Disease Activity Index of ,4 were predictive of lupus flare over the ensuing year (P = 1 × 10,4). Conclusion Monitoring serum chemokine levels in SLE may improve the assessment of current disease activity, the prediction of future disease flares, and the overall clinical decision-making. [source] TLR3 modulates immunopathology during a Schistosoma mansoni egg-driven Th2 response in the lungEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2008Amrita D. Joshi Abstract We examined the role of TLR3 in Th2-driven pulmonary granulomatous disease, using wildtype (TLR3+/+) and TLR3 gene-deficient (TLR3,/,) mice in a well-established model of Schistosoma mansoni egg-induced pulmonary granuloma. The intravenous bolus injection of S. mansoni eggs into S. mansoni -sensitized TLR3+/+ mice was associated with an increase in TLR3 transcript expression in alveolar macrophages and ex vivo spleen and lung cultures at day 8 after egg injection. Lungs from TLR3,/, mice showed an increase in granuloma size, greater collagen deposition around the granuloma, and increased Th2 cytokine and chemokine levels compared with similarly sensitized and challenged TLR3+/+ mice. Macrophages from TLR3,/, mice exhibited an M2 phenotype characterized by increased arginase and CCL2 expression. Significantly greater numbers of CD4+CD25+ T cells were present in the lungs of TLR3,/, mice compared with TLR3+/+ mice at day 8 after egg embolization. Cells derived from granulomatous lung and lung draining lymph nodes of TLR3,/, mice released significantly higher levels of IL-17 levels relative to TLR3+/+ cells. Thus, our data suggest that TLR3 has a major regulatory role during a Th2-driven granulomatous response as its absence enhanced immunopathology. [source] Microbial Toll-like receptor ligands differentially regulate CXCL10/IP-10 expression in fibroblasts and mononuclear leukocytes in synergy with IFN-, and provide a mechanism for enhanced synovial chemokine levels in septic arthritisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2003Paul Proost Abstract The CXC chemokine IFN-,-inducible protein-10 (IP-10/CXCL10) activates CXC chemokine receptor 3 (CXCR3) and attracts activated T cells and natural killer cells. Peripheral blood mononuclearcells (PBMC) produce low but significant amounts of IP-10/CXCL10 protein upon stimulation with double-stranded (ds) RNA, the Toll-like receptor 3 (TLR3) ligand. IFN-, is a superior IP-10/CXCL10inducer. The bacterial TLR4 and TLR2 ligands, LPS and peptidoglycan (PGN), inhibit IFN-,- or dsRNA-dependent IP-10/CXCL10 production in PBMC, whereas IL-8/CXCL8 production was enhanced. In fibroblasts a different picture emerges with IFN-, inducing moderate and dsRNA provoking strong IP-10/CXCL10 production. Furthermore, treatment of fibroblasts with IFN-, in combination with bacterial LPS or PGN results in a synergistic production of IP-10/CXCL10 and IL-8/CXCL8. The synergistic induction of IP-10/CXCL10 in fibroblasts is reflected by significantly enhanced IP-10/CXCL10 concentrations in synovial fluids of septic compared to osteoarthritis patients to reach on average higher levels than those of IL-8/CXCL8. These high amounts of IP-10/CXCL10 produced by connective tissue fibroblasts not only attract CXCR3 expressing activated Th1 cells and natural killer cells to sites of infection but may also antagonize the CCR3 dependent attraction of Th2 lymphocytes and exert CXCR3-independent, defensin-like antibacterial activity. [source] Selective CB1 cannabinoid receptor antagonist, SR141716A, attenuates liver injury induced by Concanavalin AHEPATOLOGY RESEARCH, Issue 4 2009Midori Kojima Aim:, The aim of this study was to investigate the hepatoprotective activity of a selective cannabinoid receptor 1 (CB1) antagonist, SR141716A, in a Concanavalin A (Con A)-induced mouse liver injury model and to determine whether SR141716A has an effect on the production of inflammatory cytokines and chemokines induced by Con A. Results:, Injection of Con A (20 mg/kg) to mice developed hepatitis determined by plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation and necrosis in the liver. Pretreatment with SR141716A (30 mg/kg) significantly reduced plasma AST and ALT level, protected against necrosis in the liver, and significantly reduced plasma cytokine and chemokine levels, including TNF,, IFN-,, CXCL9, MIP1-,, and IL-10 and no change decreased in IL-4. Conclusions:, The selective CB1 antagonist, SR141716A, exerts a hepatoprotective effect on Con A-induced liver injury in mice by attenuating the increase in cytokine and chemokine levels and inhibiting hepatocyte injury. These findings raise the possibility of using CB1 antagonists as anti-inflammatory drugs for treating hepatitis as well as other inflammatory diseases. [source] Suppression of experimental colitis in mice by CD11c+ dendritic cellsINFLAMMATORY BOWEL DISEASES, Issue 2 2009Joseph E. Qualls PhD Abstract Background: The innate immune system serves a critical role in homeostasis of the gastrointestinal (GI) tract. Both macrophages (MØs) and dendritic cells (DCs) have been shown to have pathogenic roles in animal models of inflammatory bowel disease. However, studies by several labs have established that resident MØs and DCs within the normal GI tract maintain an immunosuppressive phenotype compared to that seen in other peripheral sites. Recent studies by our lab demonstrated that the depletion of both MØs and DCs before the initiation of dextran sodium sulfate (DSS)-induced colitis resulted in exacerbation of disease, partly caused by increased neutrophil influx. Methods/Results: In this current report, DSS-induced colitis was shown to be significantly more severe when DCs were selectively depleted in mice as indicated by changes in weight loss, stool consistency, rectal bleeding, and histopathology. In contrast to enhanced colitis in MØ/DC-depleted mice, which was associated with increased neutrophil influx, increased colitis in DC-depleted mice was not associated with an increase in neutrophils in the colon, as shown by CXCL1 chemokine levels and myeloperoxidase (MPO) activity. However, increased IL-6 gene and protein expression in colon tissues correlated positively with increased colitis severity in DC-depleted mice compared to colitis in DC-intact mice. Conclusions: This study demonstrates that resident DCs can suppress the severity of acute DSS colitis and that regulation of IL-6 production may contribute to DC-mediated control of intestinal inflammation. (Inflamm Bowel Dis 2008) [source] Smoke Exposure and Ethanol Ingestion Modulate Intrapulmonary Polymorphonuclear Leukocyte Killing, but Not Recruitment or PhagocytosisALCOHOLISM, Issue 9 2006Elizabeth A. Vander Top Background: People who smoke and abuse alcohol are uniquely susceptible to pulmonary infections caused by Streptococcus pneumoniae, the pneumococcus. The primary cellular defense against pneumococci within the lungs is the polymorphonuclear leukocyte (PMN). Cigarette smoke and ethanol (EtOH) are known to alter certain PMN functions, but little is known about their concurrent effects. Methods: Male Sprague,Dawley rats were exposed twice daily for 8 weeks to cigarette smoke (smoke-exposed) or room air (sham-exposed). During the final week of exposure, the rats were pair-fed a liquid diet containing either 36 or 0% EtOH calories. Polymorphonuclear leukocytes were prerecruited into the rats' lungs by transtracheal injection of lipopolysaccharide. Five hours later, the rats were infected transtracheally with S. pneumoniae, and PMN recruitment, phagocytosis, and bactericidal activity were quantified within their lungs. Chemokine levels were also measured in bronchoalveolar lavage fluids, lung homogenates, and sera. Results: Neither PMN recruitment nor phagocytic uptake of pneumococci was altered by EtOH ingestion or smoke exposure. Killing of the organisms, however, was significantly decreased in sham-exposed, but not smoke-exposed, rats ingesting EtOH. Parallel results were determined for serum cytokine-induced neutrophil chemoattractant-1 (CINC-1), with EtOH ingestion significantly decreasing the levels in sham-exposed, but not smoke-exposed, rats. Pulmonary levels of macrophage inflammatory protein-2 (MIP-2) and CINC-1 were highly elevated by the combination of EtOH and smoke. Conclusions: One week of EtOH ingestion by rats impaired the ability of their PMNs to kill S. pneumoniae within their lungs. This was not due to decreased recruitment of the PMNs to the lungs or to diminished phagocytosis of intrapulmonary pneumococci. The addition of twice-daily cigarette smoke exposure to this short-term EtOH ingestion model restored PMN bactericidal ability to levels observed in the absence of either treatment. These EtOH-induced and smoke-induced alterations in PMN killing may be related to alterations in both pulmonary and systemic inflammatory chemokine levels. [source] Oxidative stress due to anesthesia and surgical trauma: Importance of early enteral nutritionMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 6 2009Katerina Kotzampassi Abstract Anesthesia and surgical trauma are considered major oxidative and nitrosative stress effectors resulting in the development of SIRS. In this study we evaluated the usefulness of early enteral nutrition after surgical trauma. Sixty male Wistar rats were subjected to midline laparotomy and feeding-gastrostomy. Twenty of these rats served as controls after recovering from the operation stress. The remaining rats received, through gastrostomy, enteral nutrition or placebo-feeding for 24 h. Oxidative stress markers and CC chemokine production were evaluated in rat serum and liver tissue. The operation itself was found to increase nitric oxide (NO) and malondialdehyde (MDA) and to decrease superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as liver tissue energy charge (EC) in relation to controls. The rats receiving enteral feeding exhibited statistically significantly lower levels of NO and MDA, and higher levels of SOD, GSH-Px, and liver EC, in relation to placebo feeding rats. The operation significantly increased the chemokines monocyte chemoattractant protein (MCP)-1 and regulated upon activation, normal T-cell expressed, and secreted (RANTES) in rat serum, while enteral nutrition caused a further significant increase in chemokine levels in serum. mRNA chemokine expression in liver was increased in a similar pattern. These findings indicate that early enteral feeding might play an important role after surgery ameliorating oxidative stress, affecting positively the hepatic EC and regulating, via chemokine production, cell trafficking, and healing process. [source] Serum concentration of macrophage-derived chemokine may be a useful inflammatory marker for assessing severity of atopic dermatitis in infants and young childrenPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 4 2003Ting Fan Leung Chemokines are responsible for the trafficking of leukocytes to sites of inflammation. Serum chemokine levels were previously shown to be increased in adult patients with atopic dermatitis (AD). We tested whether serum concentrations of chemokines, including macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC), eotaxin (EOX), interferon gamma inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1), are useful inflammatory markers for assessing AD severity in infants and young children. To investigate this, we assessed the severity of AD clinically using the SCORing Atopic Dermatitis (SCORAD) index system. Serum chemokine concentrations were determined by sandwich enzyme immunoassay. Twenty AD patients with a median age of 2.1 years [interquartile range (IQR): 0.6,4.2] were recruited. Their SCORAD score was 23.5 (12.5,33.5). Serum concentrations of MDC, TARC, EOX, IP-10 and MCP-1 were 2551 (1978,3935), 1469 (1125,3070), 68 (57,85), 126 (101,226) and 518 (419,614) pg/ml, respectively. Serum MDC levels correlated with SCORAD (r =,0.608, p = 0.004) and its extent (r =,0.629, p = 0.003) and intensity (r =,0.557, p = 0.011) components. Serum TARC concentration showed weaker correlation with extent (r =,0.474, p = 0.035) and intensity (r =,0.465, p = 0.039) of skin involvement but not SCORAD. The median serum levels of MDC (3131 vs. 2394 pg/ml; p = 0.031) and EOX (80 vs. 61 pg/ml; p = 0.046) were also higher in children with moderate as compared with mild AD. The other chemokines did not correlate with AD severity. In conclusion, our results suggest that serum MDC concentration may be a useful inflammatory marker for assessing AD severity in infants and young children. [source] ORIGINAL ARTICLE: Effects of Peritoneal Fluid from Endometriosis Patients on Interferon-,-Induced Protein-10 (CXCL10) and Interleukin-8 (CXCL8) Released by Neutrophils and CD4+ T CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2009Ji-Yeon Kim Problem, Intraperitoneal immuno-inflammatory changes may be associated with the pathogenesis of endometriosis. We evaluated the effects of peritoneal fluid obtained from patients with endometriosis (ePF) on the release of interferon-,-induced protein-10 (IP-10/CXCL10) and interleukin-8 (IL-8/CXCL8) by neutrophils, CD4+ T cells, and monocytes. Method of study, Neutrophils, CD4+ T cells, and monocytes were cultured with ePF and the chemokine levels in the supernatants were then measured using enzyme-linked immunosorbent assay. Results, The addition of ePF to cultures of CD4+ T cells led to a significant increase in the release of IP-10 when compared with control PF without endometriosis (cPF). There was a positive correlation between the levels of IL-8 and IP-10 in ePF (R = 0.89, P = 0.041), but not between the levels of IP-10 and IL-8 released by neutrophils, CD4+ T cells, and monocytes. The levels of IP-10 in ePF were positively correlated with the release of IP-10 by ePF-treated neutrophils (R = 0.89, P < 0.001), CD4+ T cells (R = 0.93, P < 0.001), and monocytes (R = 0.70, P = 0.01). Moreover, the addition of ePF significantly enhanced the interferon-,-induced release of IP-10 by nuetrophils and CD4+ T cells. Conclusion, These findings suggest that neutrophils and T cells release differential levels of IP-10 and IL-8 in response to stimulation with ePF, and that these cells are a major source of IP-10 in the PF of endometriosis patients. [source] Interferon-regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: A validation studyARTHRITIS & RHEUMATISM, Issue 10 2009Jason W. Bauer Objective Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by unpredictable flares of disease activity and irreversible damage to multiple organ systems. An earlier study showed that SLE patients carrying an interferon (IFN) gene expression signature in blood have elevated serum levels of IFN-regulated chemokines. These chemokines were associated with more-severe and active disease and showed promise as SLE disease activity biomarkers. This study was designed to validate IFN-regulated chemokines as biomarkers of SLE disease activity in 267 SLE patients followed up longitudinally. Methods To validate the potential utility of serum chemokine levels as biomarkers of disease activity, we measured serum levels of CXCL10 (IFN,-inducible 10-kd protein), CCL2 (monocyte chemotactic protein 1), and CCL19 (macrophage inflammatory protein 3,) in an independent cohort of 267 SLE patients followed up longitudinally over 1 year (1,166 total clinic visits). Results Serum chemokine levels correlated with lupus activity at the current visit (P = 2 × 10,10), rising at the time of SLE flare (P = 2 × 10,3) and decreasing as disease remitted (P = 1 × 10,3); they also performed better than the currently available laboratory tests. Chemokine levels measured at a single baseline visit in patients with a Systemic Lupus Erythematosus Disease Activity Index of ,4 were predictive of lupus flare over the ensuing year (P = 1 × 10,4). Conclusion Monitoring serum chemokine levels in SLE may improve the assessment of current disease activity, the prediction of future disease flares, and the overall clinical decision-making. [source] Serum chemokine profile in patients with bullous pemphigoidBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2007H. Nakashima Summary Background, Bullous pemphigoid (BP) is an autoimmune inflammatory disease causing blister formation at the dermoepidermal junction. Cutaneous infiltration of activated CD4+ T cells and eosinophils is an early event in blister formation during the disease process, suggesting that the trafficking of circulating leucocytes through the sites of inflammation is crucial in the pathogenesis of the disease. While the accumulated evidence suggests that some cytokines are involved in the pathogenesis, there have been few reports about serum chemokine profiles in patients with BP. Objectives, To determine serum profiles of various chemokines and their clinical association in patients with BP. Methods, Concentrations of 10 chemokines , interferon (IFN)- , -inducible protein-10 (IP-10), monokine induced by IFN- , (MIG), macrophage inflammatory protein (MIP)-1,, MIP-1,, RANTES, eotaxin, monocyte chemoattractant protein (MCP)-1, MCP-2, MCP-3 and growth-regulated oncogene- ,, were measured in serum samples from 38 patients with BP, 16 with pemphigus vulgaris (PV) and 17 normal controls using a sandwich immunoassay-based multiplex protein array system. Results, While there was no significant increase in any serum chemokine levels in patients with PV, serum levels of IP-10 and MCP-1 were significantly increased in patients with BP compared with healthy controls. Furthermore, serum levels of IP-10, MIG, MCP-1 and eotaxin in patients with BP increased significantly with disease severity as determined by the area affected. Conclusions, These observations suggest that an elaborately orchestrated network of chemokines, especially MCP-1 and IP-10, contributes to the pathomechanism of BP. [source] Serum chemokine levels in Hodgkin lymphoma patients: highly increased levels of CCL17 and CCL22BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2008Marijke Niens Summary Hodgkin lymphoma (HL) is characterized by a minority of neoplastic Hodgkin-Reed Sternberg (HRS) cells surrounded by a non-neoplastic reactive infiltrate. As immunological mechanisms appear to be crucial in classical HL pathogenesis, altered serum chemokine levels might be related to disease activity. Serum levels of nine chemokines were examined in 163 untreated HL patients and 334 controls. We investigated single nucleotide polymorphisms (SNPs) for association with serum CCL17 (thymus and activation-regulated chemokine, TARC) levels and HL susceptibility. Serum CCL17 and CCL22 (macrophage-derived chemokine, MDC) levels were significantly increased in 82% and 57% of the HL patients. Nodular sclerosis cases showed increased serum CCL17 and CCL22 levels (P < 0·001) and serum levels were correlated with Ann Arbor stage. Of nine patients with pre- and post-treatment serum samples, the majority showed decreased CCL17 and CCL22 levels after treatment. HRS cells expressed CCL17 and CCL22 in 77% and 75% of 74 cases. Three SNPs showed a trend of increased serum CCL17 levels with minor alleles in controls, but were not associated with HL susceptibility. CCL17 and CCL22 were the only chemokines with increased serum levels in the vast majority of HL patients, which provides further insight into the molecular mechanism(s) leading to infiltrations of reactive lymphocytes in HL. [source] ORIGINAL ARTICLE: Activation of TLR3 in the Trophoblast is Associated with Preterm DeliveryAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2009Kaori Koga Problem, Toll-like receptors (TLRs) recognize conserved sequences on the surface of pathogens and trigger effector cell functions. Previously, we described the expression of TLR3 by human trophoblast and their ability to respond to (Poly[I:C]). Here we evaluate the effect of Poly[I:C] on mouse pregnancy and characterize the local and systemic response. Method of study, C57B/6 wild type (wt) and TLR3 knockout (TLR3KO) mice were treated with Poly[I:C] at 16.5 dpc and pregnancy outcome recorded. Morphologic changes, cytokines and chemokines levels in blood and utero-placental tissue were determined. NF-,B pathway was evaluated in vivo and in vitro. Results, Poly[I:C] in C57B/6 wt mice caused preterm delivery within 24 hr (4.5 mg/kg). No effect was observed in TLR3KO mice. In addition, we observed local (placenta) and systemic (serum) response characterized by increased production of proinflammatory cytokines and chemokines. The NF-,B pathway was activated by Poly[I:C] in human and mice trophoblast cells. Conclusion, We report that Poly[I:C] induces preterm delivery via TLR3-dependent manner. Furthermore, we demonstrate that the trophoblast is able to recognize Poly[I:C] through TLR3 and respond to viral infection, modulating the immune system at the feto-maternal interface. [source] | ||||||||||