Exploratory Study of Intracutaneous Histamine Stimulation in Patient Populations with Chronic Pruritus.

Chronic pruritus can be a diagnostic sign of an underlying disease. In the intracutaneous histamine test, histamine (one of the best-known inducers of pruritus) may cause different reaction patterns depending on the underlying disease. The aim of this study was to determine if an intracutaneous injection of histamine can differentiate between the causes of chronic pruritus and thus be used as a diagnostic test in chronic pruritus of unknown aetiology.

CcpA Affects Infectivity of in a Hyperglycemic Environment.

Many bacteria regulate the expression of virulence factors via carbon catabolite responsive elements. In Gram-positive bacteria, the predominant mediator of carbon catabolite repression is the catabolite control protein A (CcpA). Hyperglycemia is a widespread disorder that predisposes individuals to an array of symptoms and an increased risk of infections.

The catabolite control protein E (CcpE) affects virulence determinant production and pathogenesis of Staphylococcus aureus.

Carbon metabolism and virulence determinant production are often linked in pathogenic bacteria, and several regulatory elements have been reported to mediate this linkage in Staphylococcus aureus. Previously, we described a novel protein, catabolite control protein E (CcpE) that functions as a regulator of the tricarboxylic acid cycle. Here we demonstrate that CcpE also regulates virulence determinant biosynthesis and pathogenesis.

Immune suppression via glucocorticoid-stimulated monocytes: a novel mechanism to cope with inflammation.

Glucocorticoids (GCs) are used as first-line therapies for generalized suppression of inflammation (e.g., allergies or autoimmune diseases), but their long-term use is limited by severe side effects.

Highly shifted proton MR imaging: cell tracking by using direct detection of paramagnetic compounds.

Purpose: To explore the feasibility of tracking thulium (Tm)-1,4,7,10-tetraazacyclododecane-α,α',α'',α'''-tetramethyl-1,4,7,10-tetraacetic acid (DOTMA)-labeled cells in vivo by means of highly shifted proton magnetic resonance (MR) imaging as a potential alternative to established cell-tracking methods.

Materials And Methods: All animal experiments were approved by the local ethics committee for animal experiments. Highly shifted proton MR imaging is based on the principle that the shifted resonances on Tm and dysprosium (Dy)-DOTMA can be detected separately from the tissue water signal at MR imaging with very short echo time and radial center-out readout (UTE, or "ultrashort echo time").

Myeloid-related proteins 8 and 14 contribute to monosodium urate monohydrate crystal-induced inflammation in gout.

Objective: Monosodium urate monohydrate (MSU) crystal-induced interleukin-1β (IL-1β) secretion is a critical factor in the pathogenesis of gout. However, without costimulation by a proIL-1β-inducing factor, MSU crystals alone are insufficient to induce IL-1β secretion. The responsible costimulatory factors that act as a priming endogenous signal in vivo are not yet known.

Epidermal expression of I-TAC (Cxcl11) instructs adaptive Th2-type immunity.

To decipher early promoters of the local microenvironment for Th2-type immunity, we wanted to identify gene patterns that were induced by Leishmania major in the infected skin of susceptible, Th2-prone BALB/c, but not of resistant, Th1-prone C57BL/6 mice. We found a marked up-regulation of the chemokine I-TAC (Cxcl11) during the first 2 d of infection in the epidermis of susceptible but not of resistant mice. Accordingly, local injection of I-TAC (2×1 μg) in resistant mice on the first day of infection resulted in a Th2-driven, sustained deterioration of disease and dramatically enhanced parasite levels.

Bacteria tracking by in vivo magnetic resonance imaging.

Background: Different non-invasive real-time imaging techniques have been developed over the last decades to study bacterial pathogenic mechanisms in mouse models by following infections over a time course. In vivo investigations of bacterial infections previously relied mostly on bioluminescence imaging (BLI), which is able to localize metabolically active bacteria, but provides no data on the status of the involved organs in the infected host organism. In this study we established an in vivo imaging platform by magnetic resonance imaging (MRI) for tracking bacteria in mouse models of infection to study infection biology of clinically relevant bacteria.

Staphylococcus aureus Panton-Valentine leukocidin induces an inflammatory response in human phagocytes via the NLRP3 inflammasome.

The Staphylococcus aureus pore-forming toxin PVL is most likely causative for life-threatening necrotizing infections, which are characterized by massive tissue inflammation and necrosis. Whereas the cytotoxic action of PVL on human neutrophils is already well established, the PVL effects on other sensitive cell types, such as monocytes and macrophages, are less clear. In this study, we used different types of human leukocytes (neutrophils, monocytes, macrophages, lymphocytes) to investigate cell-specific binding of PVL subunits and subsequent proinflammatory and cytotoxic effects.

Induction of an anti-inflammatory human monocyte subtype is a unique property of glucocorticoids, but can be modified by IL-6 and IL-10.

Glucocorticoids (GC) are the most widely used immunosuppressive agents in clinical medicine. Recently we showed that GC enhance survival of human monocytes and induce a specific anti-inflammatory monocyte subtype which actively induces resolution of inflammation. We now investigated if cytokines IL-4, IL-6 and IL-10, which, like GC, have mostly anti-inflammatory effects on macrophages, would have GC-like effects also on monocytes.

Subcutaneous infection with S. aureus in mice reveals association of resistance with influx of neutrophils and Th2 response.

Staphylococcus aureus is the leading cause of bacterial skin infection. Once it overcomes the epithelial barrier, it either remains locally controlled or spreads in the dermis causing soft tissue infection. These different courses depend not only on its virulence factors, but also on the immune response of the infected individual.

Keratinocytes determine Th1 immunity during early experimental leishmaniasis.

Experimental leishmaniasis is an excellent model system for analyzing Th1/Th2 differentiation. Resistance to Leishmania (L.) major depends on the development of a L.

LFA-1 contributes to signal I of T-cell activation and to the production of T(h)1 cytokines.

The beta(2) integrins are important for both transendothelial migration of leukocytes and T-cell activation during antigen presentation. In T cells, triggering of leukocyte functional antigen-1 (LFA-1) is required for full activation and T-helper (Th)1/Th2 differentiation. We used CD18-deficient (CD18(-/-)) mice to examine the role of LFA-1 in the activation of T cells.