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H-U Simon

Publications and source records attributed to H-U Simon.

12 recordsLinked to original sources
PubMed2007

[Anti-interleukin-5 therapy for eosinophilic diseases].

In a number of diseases with eosinophilia, elevated interleukin (IL)-5 levels are detected in the peripheral blood and/or tissues. IL-5 plays an important role in regulating the production, differentiation, recruitment, activation, and survival of eosinophils. Therefore, neutralizing IL-5 by blocking antibodies seems a promising approach in the treatment of eosinophilic diseases. Clinical trials have demonstrated that anti-IL-5 therapy results in a rapid decrease in peripheral blood eosinophil numbers. Moreover, improvement of symptoms in patients with lymphocytic variants of hypereosinophilic syndromes, in eosinophilic esophagitis and chronic rhinitis with nasal polyposis has been observed. In contrast, in patients with bronchial asthma or atopic eczema, anti-IL-5 therapy showed only moderate or no clinical effects. Future studies will have to identify those eosinophilic diseases in which anti-IL-5 antibodies are effective, perhaps with the help of newly developed biomarkers.

Animals↗
PubMed2006

Targeting survivin via PI3K but not c-akt/PKB by anticancer drugs in immature neutrophils.

Myelosuppression is the most common unwanted side effect associated with the administration of anticancer drugs, and infections remain a common cause of death in chemotherapy-treated patients. Several mechanisms of the cytotoxicity of these drugs have been proposed and may synergistically operate in a given cell. Survivin expression has been associated with cancer, but recent reports suggest that this molecule is also expressed in several immature and mature hematopoietic cells. Here, we provide evidence that treatment of immature neutrophils with anticancer drugs reduced endogenous survivin levels causing apoptosis. The anticancer drugs did not directly target survivin, instead they blocked the activity of phosphatidylinositol-3-OH kinase, which regulated survivin expression and apoptosis in these cells. Strikingly, and in contrast to other cells, this pathway did not involve the serine/threonine kinase c-akt/PKB. Moreover, in combination with anticancer drug therapy, rapamycin did not induce increased myelosuppression in an experimental lymphoma mouse model. These data suggest that drugs that block either c-akt/PKB or signaling molecules located distal to c-akt/PKB may preferentially induce apoptosis of cancer cells as they exhibit no cytotoxicity for immature neutrophils.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2006

Themes in allergy.

Explore the source record for details and available documents.

Developed Countries↗
PubMed2006

Eosinophilic esophagitis in adults--no clinical relevance of wheat and rye sensitizations.

BACKGROUND: Eosinophilic esophagitis (EE) is often associated with concomitant atopic diseases. In children with EE in whom food allergens have been identified as causative factors, elemental and elimination diets result in an improvement or resolution of symptoms. Most adult EE patients are sensitized to aeroallergens, which cross-react with plant-derived food allergens, most commonly to grass pollen and cereals. AIMS OF THE STUDY: To investigate the clinical relevance of the sensitization to wheat and rye, and the efficacy of an allergen-specific elimination diet in adult EE patients. METHODS: Six patients (five men, one women) with permanently active EE sensitized to grass pollen and the cereals wheat and rye underwent a double-blind placebo-controlled food challenge and were kept on an elimination diet avoiding wheat and rye for 6 weeks. RESULTS: The challenge tests with wheat and rye did not provoke any EE symptoms in all patients. The elimination diet failed in reducing disease activity. Although one patient noticed an improvement of symptoms, endoscopic and histopathologic findings remained unchanged. CONCLUSIONS: In adult EE patients, sensitization to wheat and rye does not seem causative for EE. Elimination diet is not a reliable and efficient therapeutic measure in EE patients sensitized to wheat and rye. Low specific immunoglobulin-E levels to wheat and rye may be a consequence of the underlying grass pollen allergy.

Adult↗
PubMed2005

Bullous delayed pressure urticaria: pathogenic role for eosinophilic granulocytes?

Bullous delayed pressure urticaria (DPU) is a rare variant of DPU. Treatment of DPU is difficult and the underlying pathogenic mechanism of DPU remains elusive. We report a 72-year-old man with DPU and associated chronic urticaria as well as delayed urticarial dermographism. Pressure challenge gave rise to a deep weal covered by multiple vesicles and bullae after 24 h. Histological examination of a skin biopsy specimen obtained 24 h after pressure challenge demonstrated intraepidermal bullae filled with eosinophils accompanied by a dense, predominantly eosinophilic infiltrate in the dermis. Whereas the numbers and morphology of mast cells were unaltered, the extracellular deposition of eosinophil cationic protein revealed evidence for eosinophil activation. Concomitantly, both CD4+ and CD8+ T lymphocytes were present in the infiltrate and expressed interleukin 5. As bullous DPU may represent the maximal variant of DPU, the investigation of the cellular infiltrate and the chemokines/cytokines released may reveal potential pathogenic mechanisms. A possible effector role of eosinophilic granulocytes, T-cell subsets and mast cells is discussed.

Aged↗
PubMed2005

Inflammatory cell numbers and cytokine expression in atopic dermatitis after topical pimecrolimus treatment.

BACKGROUND: In several clinical trials the topical application of pimecrolimus was shown to be effective in the treatment of atopic dermatitis (AD). By targeting calcineurin-dependent signaling pathways, pimecrolimus controls cytokine gene expression. The purpose of this study was to investigate the effect of pimecrolimus on the inflammatory infiltrate and cytokine expression pattern in AD upon topical therapy. METHODS: From 10 patients with acute AD, skin biopsies as well as immunophenotype and cytokine production of peripheral blood mononuclear cells (PBMC) were examined before and 3 weeks after therapy. RESULTS: The clinical improvement was associated with a marked regression of histopathological features. In particular, the density of the inflammatory infiltrate mostly containing lymphocytes and eosinophils declined. By double immunofluorescent staining, a reduced expression of the T helper (Th) 2 cytokines interleukin (IL)-5, IL-10, and IL-13 in both CD4+ and CD8+ T cells was demonstrated after therapy. Pimecrolimus therapy was also associated with a reduced expression of the Th1 cytokine interferon (IFN)-gamma. Interestingly, the numbers of epidermal CD1a+ dendritic cells increased following treatment. In the peripheral blood, a decrease of lymphocytes and eosinophils was noticed, but the distribution of lymphocyte subpopulations and their capacity of cytokine production did not change. CONCLUSIONS: Topical pimecrolimus exhibits anti-inflammatory effects in AD by reducing the inflammatory cell infiltrate and cytokine expression in the dermis.

Administration, Topical↗
PubMed2004

The physiological and pathophysiological roles of eosinophils in the gastrointestinal tract.

Eosinophils and the gastrointestinal tract interact in an intimate and enigmatic relationship. Under healthy conditions, the presence of eosinophils is limited almost exclusively to the digestive tract mucosa where they exert several effector and immunoregulatory functions. While their precise function in the gastrointestinal tract is not completely understood, it is likely that, together with different T cell subsets, eosinophils are involved in maintaining the immunologic homeostastis across the mucosal barrier under resting conditions. Eosinophils also play a role in several inflammatory conditions, such as intestinal infections, hypersensitivity reactions, primary eosinophilic inflammations and several other chronic intestinal disorders. Depending on the responsible trigger, their effects may be beneficial or detrimental. Here, we discuss the available information regarding the physiological and pathological functions of eosinophils within the gastrointestinal tract.

Digestive System↗
PubMed2004

Eosinophils and atopic dermatitis.

In spite of the progress regarding the description of immunological phenomena associated with atopic dermatitis (AD), the pathogenesis of this disease still remains unclear. The presence of eosinophils in the inflammatory infiltrate of AD has long been established. Eosinophil numbers as well as eosinophil granule protein levels in peripheral blood are elevated in most AD patients and appear to correlate with disease activity. Moreover, eosinophil granule proteins, which possess cytotoxic activity, are deposited in the skin lesions. These observations indicate a role of eosinophils in the pathogenesis of AD. Furthermore, AD is associated with increased production of T helper 2 cytokines including interleukin (IL)-5, which specifically acts on eosinophils, resulting in accelerated eosinophilopoiesis, chemotaxis, cell activation, and delayed apoptosis. Therefore, IL-5 is an interesting target for experimental therapy in this inflammatory disorder of the skin. Such studies might result in new insights into the pathogenetic role of eosinophils in AD.

Chemokine CCL11↗
PubMed2003

Clinical and immunological effects of low-dose IFN-alpha treatment in patients with corticosteroid-resistant asthma.

BACKGROUND: Interferon (IFN)-alpha is a cytokine that possesses potent anti-viral and immunoregulatory activities. We aimed to assess clinical and immunological effects of low-dose IFN-alpha in patients with severe corticosteroid-resistant asthma with and without Churg-Strauss syndrome. There is currently no efficient pharmacological treatment available for this group of patients. METHODS: We studied 10 patients with corticosteroid-resistant asthma, in which 3x10(6) IU/day IFN-alpha were administrated in addition to the prednisone dose given already before introduction of the cytokine therapy. The prednisone dose was gradually reduced dependent on the clinical situation and used as a clinical readout to evaluate the efficacy of the cytokine therapy. To distinguish between IFN-alpha- and prednisone-mediated immunological changes, the corticosteroid dose was kept constant for at least 2 weeks upon introduction of the cytokine therapy in seven patients. The effects of treatment on clinical and immunological parameters were measured at 2-4 weeks and 5-10 months depending on the availability of the patient. RESULTS: Interferon-alpha treatment rapidly improved the clinical situation as assessed by lung function parameters and required prednisone dose. Important immunological changes included: decreased leukocyte numbers, increased relative numbers of CD4+ T cells, increased differentiation of T helper (Th)1 cells, and increased expression of interleukin (IL)-10 in peripheral blood mononuclear cells. CONCLUSION: Interferon-alpha treatment was associated with dramatic improvements in the condition of patients with corticosteroid-resistant asthma with and without Churg-Strauss syndrome. Potential mechanisms of action include the establishment of a correct Th1/Th2 balance and the induction of the anti-inflammatory IL-10 gene.

Adrenal Cortex Hormones↗
PubMed2002

Peripheral blood mononuclear cells from IgE- and non-IgE-associated allergic atopic eczema/dermatitis syndrome (AEDS) demonstrate increased capacity of generating interleukin-13 but differ in their potential of synthesizing interferon-gamma.

BACKGROUND: A subgroup of patients with allergic atopic eczema/dermatitis syndrome (AEDS) are known to have normal total and specific IgE levels and negative skin prick tests towards common environmental allergens. This form of the disease has been termed non-IgE-associated allergic AEDS. Although allergic mechanisms appear to be important, the pathogenesis of both IgE- and non-IgE-associated forms of the disease is unknown. METHODS: We have compared the cytokine production pattern of peripheral blood mononuclear cells (PBMC) from IgE-associated AEDS, non-IgE-associated AEDS, and normal control individuals. PBMC were stimulated with anti-CD3 and/or anti-CD28 monoclonal antibodies (mAb) and cytokine production was measured by immunoassays in supernatants of 24-h cultures. RESULTS: Compared to healthy subjects and non-IgE-associated AEDS patients, stimulated PBMC from IgE-associated AEDS patients produced less interferon (IFN)-gamma. However, stimulated PBMC from both IgE-associated AEDS and non-IgE-associated AEDS patients produced more interleukin (IL)-13 than PBMC from control individuals. Moreover, IL-5 production was significantly increased in non-IgE-associated AEDS but not in IgE-associated AEDS patients. CONCLUSIONS: The underlying mechanism leading to increased differentiation of T helper (Th) 2 cells may involve a deficient capacity in producing IFN-gamma in IgE-associated AEDS but not in non-IgE-associated AEDS patients. IL-13 may be a key cytokine in the pathogenesis of both allergic forms of AEDS.

Adult↗
PubMed2002

Petasins in the treatment of allergic diseases: results of preclinical and clinical studies.

Plant extracts are causing an increased interest in the treatment of many chronic diseases, including asthma and other allergic diseases. Several laboratories characterized petasins (petasin, isopetasin, and neopetasin) isolated from extracts of butterbur (Petasites hybridus) as pharmacologically active components, which inhibit leukotriene synthesis in leukocytes. The molecular mechanisms by which petasins abrogate inflammatory effector cell functions have, at least partially, been identified. In vitro studies revealed that petasins may have several intracellular targets and this may depend on the stereoisomer used. In an open clinical trial in patients suffering from allergic rhinitis, a reduction of leukotriene and histamine levels in nasal fluids was associated with the butterbur extract administration. To better evaluate the clinical value in this particular allergic disease, the clinical efficacy of the drug was compared with an established antihistamine treatment scheme in a double-blind study; no significant difference was observed between the two treatment groups. In this article, we critically review recently published work and summarize the current stage in the pharmacological characterization of butterbur extracts.

Asteraceae↗