Search PubMed⌕ Search

Biomedical subjects

Margitta Worm

Publications and source records attributed to Margitta Worm.

30 records · Page 2Linked to original sources
PubMed2003

[Topical immunomodulators for treatment of eczema].

Anti-inflammatory treatment of eczematous skin diseases like atopic dermatitis and allergic contact dermatitis has mainly been performed with topical glucocorticosteroids. Increasing knowledge of the pathophysiological interactions and the immunological mechanisms during the chronic inflammatory processes in the skin offers new therapeutical options. In this review, new therapeutical approaches for the treatment of eczematous skin disease will be presented. These novel compounds include the topical immunomodulators, tacrolimus and pimecrolimus. Such molecules inhibit intracellular signal transducing phosphatases and act consecutively at the molecular level by inhibiting the activation of transcription factors. Secondly, the development of nuclear hormone receptor family members, such as retinoids, vitamin D and peroxisome proliferator-activated receptor agonists, is discussed. Substances from this family have differentiating, antiproliferative, but also immuno-modulatory effects, which make them attractive as anti-eczematous therapeutic compounds. The diversity of these interactions is extensive, and clinical studies will prove their clinical efficacy.

Adjuvants, Immunologic↗
PubMed2003

Retinoid- and carotenoid-enriched diets influence the ontogenesis of the immune system in mice.

Vitamin A (VA) has been identified as an important factor for the development of the immune system, especially during ontogenesis. It has been shown that antibody secretion and proliferation of lymphocyte populations depend on retinoids. In the present study we investigated the influence of a base VA diet and diets enriched with VA, beta-carotene and lycopene, on the ontogenesis of the immune system in mice. We examined the absolute and relative concentrations of splenic B lymphocytes (CD45R/B220), T lymphocytes (CD3+) and their subpopulations (CD4+ and CD8+), and measured serum immunoglobulin G (IgG) concentrations in the offspring of supplemented dams at different ages (1, 3, 5, 7, 14, 21 and 65 days). The experimental diets resulted in higher numbers of T and B lymphocytes after VA and carotenoid enrichment, when compared, at various time-points, with the base diet. Higher values of total serum IgG were found in the beta-carotene-enriched diet group on day 7. On days 7 and 14, the enriched diets induced significant alterations in the percentages and total numbers of splenic lymphocytes in comparison to the base diet. Our results confirm that supplementation with VA and carotenoids affect the immune-cell function during ontogenesis and suggest a possible role of these nutritional factors on the development of the immune system.

Animals↗
PubMed2003

Inhibition of IgE-production by peroxisome proliferator-activated receptor ligands.

In this study we analyzed the effect of peroxisome proliferator-activated receptor-alpha and -gamma ligands on immunoglobulin synthesis and cytokine production in non-allergic and atopic dermatitis donors in vitro, but also in vivo ovalbumin-sensitized mice. A significant inhibition in CD40+ interleukin-4-mediated, but also basal IgE synthesis from peripheral blood mononuclear cells of atopic dermatitis donors was observed in the presence of the peroxisome proliferator-activated receptor-alpha ligand (up to 47+/-12%) and peroxisome proliferator-activated receptor-gamma ligand (69+/-5%). By contrast, the production of other isotypes such as IgA, IgG, and IgM was only modest inhibited. Analysis of cytokine production from the peripheral blood mononuclear cells shows inhibition of several cytokines by both peroxisome proliferator-activated receptor ligands. The most inhibitory effect on cytokine production was observed by the peroxisome proliferator-activated receptor-gamma ligand in peripheral blood mononuclear cells from atopic dermatitis donors with high IgE baseline production. Coculture experiments show that the decrease of IgE production by ciglitazone was monocyte dependent (up to 63+/-7%). Finally, in vivo experiments from ovalbumin-sensitized mice confirmed the in vitro findings showing that the interleukin-4-mediated immune response was inhibited in ciglitazone-treated mice.

Animals↗
PubMed2002

1alpha,25-dihydroxyvitamin D3 inhibits anti-CD40 plus IL-4-mediated IgE production in vitro.

In the present study, we examined whether anti-CD40+IL-4-mediated B cell proliferation and immunoglobulin synthesis is affected by vitamin D (VD) and its low-hypercalcemic analogue EB1089 in Bcells from healthy donors. Analysis of vitamin D receptor (VDR) expression showed that only anti-CD40+IL-4-stimulated, but not resting B cells express VDR. Studies on B cell proliferation revealed that anti-CD40+IL-4-mediated proliferation of B cells was not affected by VD or EB1089. By contrast, IgE synthesis was markedly inhibited by both, VD and EB1089, starting at concentrations from 10(-10) M for VD and 10(-12) M for EB1089, with maximal inhibition at 10(-6) M (VD 85.5+/-9.7%; EB1089 77.3+/-10.8%). The production of the other Ig (IgA and IgG) was not significantly inhibited by VD after anti-CD40+IL-4 stimulation, and IgM production was only slightly reduced (18.7+/-7.9%). These observations were confirmed by intracellular staining of the different isotypes in B cells after anti-CD40+IL-4 stimulation, which showed a strong reduction of IgE(+) cells in the presence of VD. Analyses of molecules that are known to affect IgE production (CD23 and IL-6) revealed that these are not involved in VD-dependent inhibition of IgE production. By contrast, epsilon germ-line transcription was inhibited by VD (41.2+/-26.1%; n=5), as was NF-kappaB (p50 and p65) protein expression in stimulated cells. These data show that VD and its analogue EB1089 inhibit IgE production of anti-CD40+IL-4-stimulated B cells in vitro. The involved mechanism includes epsilon germ-line transcription, NF-kappaB activation and switch recombination suggesting that complex mechanisms of VD action in anti-CD40+IL-4-stimulated B cells are responsible.

B-Lymphocytes↗
PubMed2002

Inhibition of IgE production by the imidazoquinoline resiquimod in nonallergic and allergic donors.

The aim of this study was to examine whether the immune modulator resiquimod, which belongs like imiquimod to the imidazoquinolines, is capable of influencing IgE synthesis. Peripheral blood mono-nuclear cells from normal donors and patients with atopic dermatitis and with seasonal allergic rhinitis were analyzed in the presence of resiquimod, anti-CD40+interleukin-4 stimulation for induction of IgE, and anti-CD40+interleukin-4 in the presence of resiquimod, respectively. Our data show that spontaneous IgE production was inhibited in the presence of resiquimod, which was strongest at 10 ng per ml in both groups of allergic patients. Inhibition of IgE production after anti-CD40+interleukin-4 stimulation in the presence of resiquimod (10 ng per ml) was comparable between all the groups. In normal donors median inhibition of IgE synthesis was 93%, in seasonal allergic rhinitis patients 77%, and in patients with atopic dermatitis 72%. In order to rule out antiproliferative effects of resiquimod, which might influence IgE production, we also studied proliferation of peripheral blood mononuclear cells from normal donors, which remained unchanged in the presence of resiquimod at 0.1-10 ng per ml but was inhibited at 100 or 1000 ng per ml. In search of possible mechanisms responsible for the observed inhibition of IgE production, we analyzed the expression and production of molecules that are known to modulate IgE production, namely CD23 and interferon-gamma. CD23 expression on B cells was lower in the presence of resiquimod (10 ng per ml) in anti-CD40+interleukin-4 stimulated cells, whereas interferon-gamma was strongly induced (4-6-fold) by resiquimod (10 ng per ml). Furthermore, by using neutralizing interferon-gamma monoclonal antibodies, we show that inhibition of IgE production occurred in an interferon-gamma-dependent manner. Taken together our results show that resiquimod is a potent modulator of IgE production in vitro in normal but also in allergic donors.

Adult↗
PubMed2002

Aromatic components of food as novel eliciting factors of pseudoallergic reactions in chronic urticaria.

BACKGROUND: Pseudoallergic reactions (PARs) against both additives and natural foods have been reported to elicit chronic urticaria, but in natural food the responsible ingredients are largely unknown. OBJECTIVE: The study was aimed at identifying novel pseudoallergens in food and focused on evaluating tomatoes, white wine, and herbs as frequently reported food items eliciting wheal responses in urticaria. METHODS: In 33 patients with chronic urticaria and PARs to food (proved by means of elimination diet and subsequent re-exposure with provocation meals), oral provocation tests were performed with field-grown tomatoes, organically grown white wine (whole food, steam distillates, and residues), oily extracts from herbs, and food additives. In addition, skin biopsy specimens from patients were studied for in vitro mast-cell histamine release with tomato distillate alone or on subsequent stimulation with anti-IgE, substance P, and C5a. RESULTS: Seventy-six percent of patients reacted to whole tomato (steam distillate, 45%; residue, 15%), 50% to food additives, 47% to herbs, and 44% to whole wine (extract, 27%; residue, 0%). Histamine, protein, and high levels of salicylate were only found in residues. The tomato distillate was further analyzed by means of mass spectroscopy, identifying low molecular-weight aldehydes, ketones, and alcohol as major ingredients. In vitro histamine release was not caused by tomato extract itself but was enhanced by means of subsequent stimulation with substance P and C5a but not by anti-IgE. CONCLUSION: Aromatic volatile ingredients in food are novel agents eliciting PARs in chronic urticaria. Histamine, salicylate, and a direct mast-cell histamine release are not involved in this reactivity to naturally occurring pseudoallergens.

Adolescent↗
PubMed2002

Wasp venom rush immunotherapy induces transient downregulation of B cell surface molecule expression.

BACKGROUND: Little is known about the involvement of B cells in venom immunotherapy (VIT). To elucidate changes in the B cell phenotype during this process, we examined the expression of several surface molecules on peripheral B cells before and during VIT. METHODS: 15 venom-allergic patients with a history of systemic reactions after a wasp sting and venom-specific skin test reactivity as well as serum IgE were investigated before VIT (day 1), 1 day after reaching a maintenance dose of 100 microg (day 6) during inpatient rush VIT, and again on day 26 during continued outpatient maintenance therapy. Changes in the serum levels of total IgE, allergen-specific IgE (sIgE) and sIgG4 were measured by ELISA. Expression of several surface molecules on double-labelled B cells was studied by flow cytometry of peripheral blood mononuclear cells. RESULTS: Levels of total IgE, sIgE and sIgG4 showed a significant increase after 26 days of VIT. On day 6, cell surface expression of HLA- II-DR, CD5, CD32 and CD54 was decreased in intensity and numbers of positive cells compared to day 1, while on day 26, expression of these molecules approached again baseline levels. Furthermore, a trend to decreased CD23 was noted on day 6. No changes were observed for CD40, CD86, CD95 and HLA-I-ABC. CONCLUSION: These data show that during initiation of rush VIT, B cell expression of surface molecules involved in T-B cell cooperation and antigen presentation is downmodulated. B cells may thus be additional direct or indirect targets of high-dose antigen therapy and contribute to the persistence of TH1 responses during maintenance VIT treatment.

Adolescent↗
PubMed2002

Role of adverse reactions to food in urticaria and exercise-induced anaphylaxis.

In urticaria, adverse reactions to food are only a frequent finding in the subset of patients with chronic continuous urticaria. Mostly these reactions are of pseudoallergic nature, directed against artificial additives as well as naturally occurring aromatic components. IgE-mediated allergic reactions are a rare cause in acute urticaria as well as in recurrent chronic urticaria. In other types of urticaria, e.g. physical urticaria, food plays hardly any role as an eliciting agent with the exception of ice-cold drinks in cold urticaria. By contrast, exercise-induced anaphylaxis is frequently food-dependent. Two subtypes are distinguished: unspecific food-dependent exercise-induced anaphylaxis (FDEIA), where the filling of the stomach independently of the kind of food ingested prior to exercise is responsible for the symptoms. In specific FDEIA, an IgE-mediated food allergy causes symptoms only in combination with exercise. In the latter group, wheat is an important allergen.

Anaphylaxis↗
PubMed2002

Novel therapies for atopic eczema.

Atopic dermatitis (AD) has been treated with topical glucocorticosteroids for decades. With the introduction of the topical immune modulators tacrolimus and pimecrolimus, a new treatment era has begun. The knowledge on pathophysiological interactions and immunological disturbances during the chronic inflammatory process in the skin has been continuously increasing and offers new therapeutical approaches. These are discussed in this review based on the current literature, my own research findings and recent patents. Development of members of the glucocortioid family such as retinoids, vitamin D and peroxisome proliferator-activated receptor agonists, are discussed. Molecules from members of this family have profound differentiating, antiproliferative, but also immunomodulatory effects, which make them attractive as anti-eczematous compounds. Furthermore, several anti-infective and antipruritic agents, and preparations which enhance thedisturbed skin barrier function in AD are presented. Phytopharmacological and miscellaneous approaches, including Chinese tea or gamma-linolenic acid, will be critically discussed. Finally, recently patented, experimental compounds are presented, which interfere with several pathways involved in the immune response of AD.

Animals↗
PubMed2002

Immunophenotypic characterization of peripheral B cells. During short-term immunotherapy with tree pollen allergoid and the immunoadjuvant monophosphoryl lipid A.

The effects of immunotherapy (IT) on the activation and functions of B cells are not well described yet. We therefore measured the expression of several surface markers on peripheral B cells during short-term IT. Twelve patients with seasonal allergic rhinoconjunctivitis, sensitized to hazel, alder, and birch pollen proven by positive history, skin test, sIgE, and nasal provocation test, were included in the study. Eight patients received short-term IT with TA tree pollen and the immunoadjuvant monophosphoryl Lipid A; 4 patients received a placebo suspension containing 2% tyrosine. After separation of PBMCs, the expression of surface molecules on peripheral B cells were analyzed by flow cytometry before the start of IT, before the 3rd injection, at the end of IT, and after the pollen season. The expression of CD23, CD54, and HLA-DR-II on CD19+ B cells decreased during IT and then increased again after the pollen season. In the placebo group, the expression of CD23, CD54, and HLA-DR-II remained unchanged during the first three measurements. After the season, the expression of CD23, CD54 and HLA-DR-II increased in both groups. CD86 expression was decreased during treatment in both groups. Although CD86 expression increased in both groups after the season, the increase was more pronounced in the placebo group. No changes in the expression of CD32, CD40, and HLA-ABC-I were registered during the study. The results show that expression of CD23, CD54, and HLA-DR-II on peripheral B cells decreases during IT, which indicates reduced B-cell activation. Whether these effects are a result of direct allergen action on the B cells or whether they are mediated by T cells and their clinical relevance remains to be elucidated.

Adjuvants, Immunologic↗