Delineation of the role of Toll-like receptor signaling during peritonitis by a gradually growing pathogenic Escherichia coli.

In a mouse model of Escherichia coli sepsis characterized by a primary peritoneal infection with 10(4) E. coli and a gradually growing bacterial load, we here show that the early cytokine response and antibacterial defense are dominated by TLR4 via a cooperative action of MyD88 and Trif. Although MyD88(-/-) mice succumbed earlier than WT mice in this E.

In vivo lipopolysaccharide exposure of human blood leukocytes induces cross-tolerance to multiple TLR ligands.

In vitro and in vivo experiments in mice have shown that exposure of cells to the TLR4 ligand LPS induces tolerance toward a second exposure to LPS and induces cross-tolerance to certain other TLR ligands. Recently, we found that LPS tolerance in experimental human endotoxemia and Gram-negative sepsis is associated with elevated levels of IL-1R-associated kinase M, an intracellular negative regulator of MyD88-dependent TLR signaling. In the present study, we investigated whether in vivo exposure of humans to LPS induces tolerance in circulating leukocytes to other TLR agonists that rely either on MyD88- dependent or on MyD88-independent signaling.

Cecal ligation and puncture induced sepsis impairs host defense against Enterococcus faecium peritonitis.

Purpose: Multiresistant and vancomycin resistant Enterococcus faecium (VRE) can cause serious infections in hospitalized patients with various co-morbid diseases. We investigated the course of VRE peritonitis after cecal ligation and puncture (CLP)-induced sepsis and compared this to sham operated mice.

Methods: Mice were subjected to CLP or sham surgery.

The acute-phase response impairs host defence against Enterococcus faecium peritonitis.

Enterococcus faecium is an emerging pathogen that causes infections in hospitalized patients with various co-morbid diseases. These underlying diseases are often associated with an acute-phase response that renders patients vulnerable to nosocomial infections. To study the influence of the acute-phase response induced by sterile tissue injury on host defence against E.

Immunosuppression associated with interleukin-1R-associated-kinase-M upregulation predicts mortality in Gram-negative sepsis (melioidosis).

Objectives: Sepsis is associated with immunosuppression (characterized by a reduced capacity of circulating monocytes to release proinflammatory cytokines), which has been implicated in late mortality. Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast Asia with a mortality of up to 40%. Previous in vitro and murine studies have suggested a key role for the so-called negative regulators of the toll-like receptor (TLR) signaling pathway in immunosuppression.

Deficiency of alpha7 cholinergic receptors facilitates bacterial clearance in Escherichia coli peritonitis.

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

Methods: To determine the role played by alpha7 receptors in antibacterial defense, peritonitis was induced in alpha7 receptor-deficient (alpha7(-/-)) and wild-type (WT) mice by intraperitoneal injection with Escherichia coli.

Results: At 20 h after infection, virtually all alpha7(-/-) mice had cleared the infection from their peritoneal cavities and had sterile blood cultures, whereas WT mice had high bacterial loads at the primary site of infection and were bacteremic.

TLR2-dependent MyD88 signaling contributes to early host defense in murine Enterococcus faecium peritonitis.

The incidence of infections with Enterococcus faecium is increasing worldwide. TLRs have been implicated in the recognition of pathogens and the initiation of an adequate innate immune response. We here sought to determine the roles of MyD88, the common adaptor protein involved in TLR signaling, TLR2, TLR4, and CD14 in host defense against E.

Effect of acute hyperglycaemia and/or hyperinsulinaemia on proinflammatory gene expression, cytokine production and neutrophil function in humans.

Aims: Type 2 diabetes is frequently associated with infectious complications. Swift activation of leucocytes is important for an adequate immune response. We determined the selective effects of hyperglycaemia and hyperinsulinaemia on lipopolysaccharide (LPS)-induced proinflammatory gene expression and cytokine production in leucocytes and on neutrophil functions.

Induction of IRAK-M is associated with lipopolysaccharide tolerance in a human endotoxemia model.

Recent in vitro and murine in vivo studies have identified several potential LPS tolerance factors. In this study, we describe the expression kinetics of these LPS tolerance factors in standardized human endotoxemia models using i.v.

Effects of prednisolone on the systemic release of mediators of cell-mediated cytotoxicity during human endotoxemia.

Corticosteroids are widely used for the suppression of cell-mediated cytoxicity. This process is mediated by natural killer cells and cytotoxic T lymphocytes, and their activation can be monitored by levels of the chemokines CXCL9 and CXCL10, the degranulation product granzymes A and B, and by levels of secretory phospholipase A2. The current study aimed to determine the effects of increasing doses of prednisolone on the release of these mediators in healthy humans exposed to LPS.

Mucolytic activity of bacterial and human chitinases.

Several pulmonary pathologies, like cystic fibrosis (CF), are characterized by hypersecretion and stasis of tenacious mucus. Bacterial glycosidases are known to degrade mucins but their use as mucolytic agents is questionable. The observation that bacterial chitinases degrade mucins and the recent discovery of human chitinases, which have been proposed to be involved in the genesis of asthma, prompted us to evaluate the mucolytic properties of human derived chitinases.

Pro-inflammatory delipidizing cytokines reduce adiponectin secretion from human adipocytes without affecting adiponectin oligomerization.

Adiponectin and, especially, its oligomeric complex composition have been suggested to be critical in determining insulin sensitivity. Pro-inflammatory cytokines play an important role in the development of insulin resistance in obesity and associated diseases. Therefore, we investigated the effect of long-term exposure of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta, and interferon (IFN)-gamma on total insulin-sensitizing adiponectin secretion and adiponectin complex formation from human adipocytes.

Prednisolone dose-dependently influences inflammation and coagulation during human endotoxemia.

The effects of steroids on the outcome of sepsis are dose dependent. Low doses appear to be beneficial, but high doses do not improve outcome for reasons that are insufficiently understood. The effects of steroids on systemic inflammation as a function of dose have not previously been studied in humans.

Cytokine-mediated modulation of leptin and adiponectin secretion during in vitro adipogenesis: evidence that tumor necrosis factor-alpha- and interleukin-1beta-treated human preadipocytes are potent leptin producers.

Over the last decade, compelling evidence has been presented that cytokines affect adipocyte tissue formation and function. In this study we explored the effect of pro-inflammatory (i.e.