Tom van der Poll

..These protective APC effects do not rely on the anticoagulant properties of this protein. APC mutants that lack anticoagulant properties but retain the capacity to activate PAR1 are promising new drugs for sepsis treatment...

..S. pneumoniae is the most common causative agent of meningitis, and is associated with high morbidity and mortality. We aimed to develop an integrated and representative pneumococcal meningitis mouse model resembling the human situation...

..The aim of this study was to determine the effect of inhalation of beta2 agonists on the host immune response to respiratory tract infection with NTHi...

..The aim of this study was to investigate FSAP activation in patients suffering from various inflammatory diseases of increasing severity...

..Likewise, the neutrophil-lymphocyte count ratio (NLCR) has been shown a simple promising method to evaluate systemic inflammation in critically ill patients...

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..We here determined the effect of the FVL mutation on coagulation, inflammation, bacterial outgrowth and outcome in murine pneumococcal pneumonia...

..We determined the impact of lethal influenza A (H1N1) infection on systemic and pulmonary coagulation and inflammation, and the effect of recombinant mouse (rm-) APC here on...

..Their main conclusion was that diabetes patients, relative to non-diabetics, were less likely to develop respiratory failure and more likely to develop renal failure during the course of sepsis...

..We evaluated the effect of nebulized anticoagulants on pulmonary coagulopathy and inflammation in a rat model of Streptococcus pneumoniae pneumonia...

..faecium strains. To investigate whether Esp facilitates bacterial adherence and intestinal colonization of E. faecium, we used human colorectal adenocarcinoma cells (Caco-2 cells) and an experimental colonization model in mice...

..Furthermore, evidence is discussed that mediators traditionally involved in the regulation of the hemostatic balance may also influence other inflammatory pathways...

..This review presents the most recent data on the crosstalk between TF-mediated coagulation and inflammation, with a specific emphasis on these processes in the lung...

..pneumoniae did not reveal an anti-inflammatory effect of nicotine either. The present data suggest that nicotine transiently impairs host defence in pneumococcal pneumonia...

..Cytokines have been implicated as important mediators in these hemostatic alterations. This article summarizes recent insights into which cytokines are likely to be involved in the procoagulant response to systemic infection...

..This Review summarises current knowledge of microbial pathogenesis and host-pathogen interactions during sepsis and the ensuing development of potential therapeutics...

..Activated protein C (APC) has systemic anticoagulant effects in patients with sepsis...

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..As a result of these studies our knowledge of the pathogenesis of sepsis has increased considerably. This review focuses on immunomodulatory strategies that have reached the phase of clinical evaluation in patients with sepsis...

..This chapter discusses key components of the pro- and anti-inflammatory response to sepsis and the regulation thereof...

..This review summarizes recently acquired knowledge on the bimodal interactions between coagulation and inflammation in infection...

..coli peritonitis. These findings identify a novel protective function of tPA in abdominal sepsis caused by E. coli that seems independent of its role in the generation of plasmin...

..Although salmeterol, a beta2-adrenoceptor agonist with profound bronchodilatory properties, has been studied extensively, the effects of this compound on the pulmonary hemostatic balance are not elucidated...

..These data indicate that the pneumococcus uses the PAFR leading to severe pneumonia in a host previously exposed to influenza A...

..In conclusion, in B. burgdorferi infection, uPAR is required for phagocytosis and adequate eradication of the spirochete from the heart by a mechanism that is independent of binding of uPAR to uPA or its role in the fibrinolytic system...

..Therefore, our data suggest that although SIGNR1 has a similar binding specificity as DC-SIGN, its role is limited during murine M. tuberculosis infection...

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..The clearance of pulmonary infection with the non-pathogenic M. smegmatis was also unaltered in LBP-/- mice. These data suggest that LBP does not contribute to an effective host response in M. tuberculosis infection...

..Together, these data indicate that the enhanced production of IL-18 in melioidosis is an essential part of a protective immune response to this severe infection...

..pseudomallei by facilitating the migration of neutrophils toward the primary site of infection and subsequently facilitating the phagocytosis of B. pseudomallei...

..Inhalation of LPS by healthy humans reproduces major features of the procoagulant response to inflammatory and infectious lung diseases and may be used as a novel model to evaluate pathogenetic mechanisms and new interventions...

..The current data demonstrate that LPS instillation in the human lung primes alveolar macrophages for further stimulation with either LPS or LTA, possibly by sustained p38 mitogen-activated protein kinase activation...

..During pneumococcal pneumonia, G-CSF is produced locally at the site of the infection, where it exerts both pro- and anti-inflammatory effects...

..We investigated the role of the protein C system in pneumonia caused by Pseudomonas aeruginosa, the organism that is predominantly involved in ventilator-associated pneumonia...

..CONCLUSIONS: These data suggest that TF-FVIIa activity contributes to activation of coagulation in the lung during pneumococcal pneumonia but does not play an important role in the antibacterial host defense in this murine model...

..These data indicate that HMGB-1 induces release of cytokines, activation of coagulation, and neutrophil recruitment in vivo via a mechanism that at least in part depends on TLR-4 and RAGE...

..These data suggest that endogenous IL-18 plays an important role in the early antibacterial host response during E. coli-induced peritonitis...

..Melioidosis is a severe infection caused by the gram-negative bacterium, Burkholderia pseudomallei, that is endemic in Southeast Asia. We aimed to characterize the expression and function of TLRs in septic melioidosis...

..These data suggest that RAGE is detrimental during IAV pneumonia...

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..We have recently shown that during melioidosis, a severe infection caused by the gram-negative bacterium Burkholderia pseudomallei, TLR2 but not TLR4 impacts the immune response of the intact host in vivo...

..These data suggest that the capacity of TM to generate APC does not play a role of importance in the pulmonary response to respiratory pathogens or LPS...

..These data suggest that LBP is important for a protective immune response in Klebsiella pneumonia, but does not contribute to an effective host response in pneumococcal pneumonia...

..Our study shows that PAI-1 is critically involved in host defense against E. coli-induced acute pyelonephritis, in part, by modulating neutrophil influx...

..These data indicate that the PAFR does not interfere with the clearance of NTHi from the respiratory tract...

..High-mobility group box 1 is a high-affinity binding ligand for the receptor for advanced glycation end products with cytokine activities and plays a role in sepsis...

..C1-inh treatment increased bacterial clearance, possibly through an up-regulation of CR3. Hence, C1-inh may be a useful agent in the treatment of pneumococcal meningitis...

..This increased susceptibility to secondary bacterial pneumonia is at least in part caused by excessive IL-10 production and reduced neutrophil function in the lungs...

..Together, these data demonstrate that TLR2 can initiate renal inflammation during progressive renal injury and that the absence of TLR2 does not affect the development of chronic renal injury and fibrosis...

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..Acinetobacter baumannii is an emerging pathogen in nosocomial pneumonia. Trauma and postsurgical patients display a profound acute-phase protein response and are susceptible to pneumonia...

..These data suggest that MCP-1 is a proinflammatory mediator during pulmonary inflammation induced by either LPS or LTA...

..This suggests a novel antagonistic role for p40 homodimers in regulating the chemotactic bioactivity of IL-12 after pulmonary mycobacterial infection...

..This study suggests that beta-adrenergic receptors, which are widely expressed in the lungs, serve as negative regulators of pulmonary cytokine release and coagulation induced by LPS and less so during LTA-induced pulmonary inflammation...

..These data argue against an important part for TAFI in the regulation of the procoagulant-fibrinolytic balance in sepsis and reveals a thus far unknown role of TAFI in the occurrence of hepatic necrosis...

..Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) is considered to be important for an appropriate immune response against pathogens that enter the lower airways...

..Activation of p38 MAPK plays an important role in the procoagulant and endothelial cell response after in vivo exposure to LPS...

..These data suggest that TLR4 plays a protective role in host defense against lung infection by M. tuberculosis...

..We aimed to characterize TREM-1 expression and function during sepsis caused by Burkholderia pseudomallei (melioidosis)...

..Pulmonary coagulopathy may contribute to an adverse outcome in lung injury. We assessed the effects of local anticoagulant therapy on bronchoalveolar and systemic haemostasis in a rat model of endotoxemia-induced lung injury...

..These data suggest that a TM mutation that impairs APC generation results in uncontrolled lung inflammation during tuberculosis...

..The receptor for advanced glycation end products (RAGE) mediates a variety of inflammatory responses...

..In conclusion, attraction of neutrophils to the primary site of E. faecium infection is important for a rapid clearance of this bacterium, thereby attenuating a systemic inflammatory response...

..We investigated the role of these natural anticoagulants in Streptococcus pneumoniae pneumonia...

..These data suggest that the MyD88-dependent pathway of TLR4 is important for an effective innate immune response to respiratory tract infection caused by NTHi...

..Levels of sICAM-1 were not affected by prednisolone. Together, the data suggest that prednisolone differentially and dose-dependently influences the release of soluble endothelial adhesion molecules during human endotoxemia...

..The mortality was significantly higher and earlier in the course of the disease in IL-1R(-/-) mice. These results demonstrate that endogenous IL-1 is required for an adequate host defense in pneumococcal meningitis...

..These data indicate that local administration of GTS-21 inhibits TNF-alpha release in the lung during LPS-induced inflammation...

..In conclusion, we identified TLR4 as a cellular sentinel for acute renal damage that subsequently controls the induction of an innate immune response...

..Inhibition of the tissue factor (TF)/factor (F) VIIa pathway has been shown to attenuate the activation of coagulation and to prevent death in a primate model of sepsis caused by gram-negative bacteria...

..kansasii. These data suggest that CD4+ cells, IFN-gamma, and an intact T helper cell type 1 response play a limited role in protective immunity against pulmonary M. kansasii infection...

..The results provide evidence that CD44 on urothelial cells facilitates E. coli UTI. Disruption of the interaction between CD44 and HA in the bladder may provide a new approach to prevent and to treat UTI...

..These data indicate that prednisolone dose-dependently and differentially influences the systemic activation of different host response pathways during human endotoxemia...

..These data indicate that the acute-phase response impairs host defence against E. faecium, suggesting that this condition may contribute to the increased vulnerability of critically ill patients to enterococcal infections...

..The efferent vagus nerve can inhibit inflammation via interaction between acetylcholine and alpha7 cholinergic receptors...

..These data suggest that type 2 diabetes patients may be especially vulnerable to prothrombotic events during inflammatory states...

..Natural inhibitors of coagulation prevent bronchoalveolar activation of coagulation, but do not induce major alterations of the pulmonary inflammatory response in rat endotoxaemia...

..IL-6 is, however, an important intermediate factor in activation of coagulation in low grade endotoxemia in chimpanzees...

..In vitro, IL-10 dose-dependently attenuated LPS-induced release of both GRO-alpha and ENA-78 in whole blood and in cultures of isolated polymorphonuclear and mononuclear cells...

..These data suggest that P-ExA impairs host defence during pneumonia caused by P. aeruginosa by a mechanism that does not involve effects on neutrophil influx, cytokines, chemokines or NO formation...

..PAF does not seem to be an important intermediate factor in endotoxin-induced neutrophilia or neutrophil degranulation...

..CONCLUSION: These data illustrate a thus far unrecognized effect of VNS and suggest that the cholinergic anti-inflammatory pathway not only impacts on inflammation but also on the coagulant-anticoagulant balance...

..These data suggest that infectious stimuli may influence monocyte function in vivo by enhancing the expression of uPAR...

..05). These results indicate the ability of erythromycin to reduce CXC chemokine production and to enhance neutrophil degranulation in human blood...

..These findings indicate that during urosepsis, the antiinflammatory cytokine response is generated predominantly at the systemic level...

..Our results indicate that tumor necrosis factor-alpha is a prime mediator of endotoxin-induced release of its own soluble receptors...

..IL-10 release elicited by injection of endotoxin is not mediated by PAF or IL6...

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..IL-8 was also recovered from mononuclear and polymorphonuclear cells. Cell-associated chemokines may more accurately reflect their production than plasma concentrations...

..coli peritonitis, it protects mice from lethality by attenuating the development of a systemic inflammatory response syndrome by a mechanism that involves inhibition of TNF release...

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..In healthy volunteers, LPS induced increases in monocyte and granulocyte uPAR and CD11b...

..Furthermore, in infected lungs, fibrinolysis was depressed, with high levels of plasminogen activator inhibitor type 1. In conclusion, ventilator-associated pneumonia is characterised by a hypercoagulant state at the site of infection...

..Thus, in contrast to CD4+ counts and neopterin levels, sTNFR concentrations, especially those of the type II STNFR, appear to be valuable surrogate markers for monitoring the efficacy of ZDV treatment in asymptomatic HIV-1 infection...

..This polymicrobial model with implicated surgical intervention reflects the clinical situation and may be more appropriate to test therapeutic interventions than a model involving only CLP...

..During urosepsis, CXC chemokines are predominantly produced within the urinary tract, where they are involved in the recruitment of neutrophils to the urinary compartment...

..The interaction between the cytokine network and granzymes may play an important immunoregulatory role during bacterial infections...

..A single oral dose of thalidomide attenuates neutrophil activation upon ex vivo stimulation with bacterial antigens...

..These data suggest that CD44 protects against hyperoxia-induced lung injury and mortality by a mechanism that at least in part relies on its ability to clear HA from the bronchoalveolar space...

..Remarkably, IFN-gammaR(-/-) mice had higher nitric oxide levels in the BALF at 24 hours after infection (P < 0.05). Endogenous IFN-gamma impairs rather than augments host defense during pneumonia caused by P. aeruginosa...

..Neutralization of the early endotoxin-induced TNF activity by anti-TNF caused a marked reduction in IL-1RA concentrations (P < .05). These results indicate that TNF is an intermediate factor in IL-1RA release in endotoxemia...