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Biomedical subjects

Alexander Kapp

Publications and source records attributed to Alexander Kapp.

35 records · Page 2Linked to original sources
PubMed2004

Chronic urticaria and infections.

PURPOSE OF REVIEW: The pathogenesis of chronic urticaria is multifactorial and a specific treatment is lacking. In acute urticaria there is no doubt of a causal relationship with infections and all chronic urticaria must start as the acute form. However, in the chronic form a primary role for infection is controversial, although it is undeniable that concurrent infections exacerbate the condition. This is the first English language review based on a detailed analysis of current peer-reviewed publications dealing with infections and chronic urticaria. RECENT FINDINGS: In chronic urticaria there is a lot of evidence for different infections, but randomized controlled trials are missing. The prevalence of infections is not increased but in susceptible patients the immune response may lead to the development of chronic urticaria. Interestingly, there is evidence for an infection-associated autoreactive response at least in the subgroup with a positive autologous serum skin test. A variety of mechanisms have been invoked to explain these observations, including molecular mimicry. SUMMARY: Actually the arguments for an important role of underlying causal infections in chronic urticaria are weak, from an evidence-based viewpoint, but there are data suggesting a link. Moreover, an association with underlying or precipitating infectious causes is difficult to establish because there is no possibility for challenge and the number of other urticarial triggers is vast. For the future it will be necessary to reveal the link between urticaria, autoreactivity, non-immunoglobulin E-mediated hypersensitivity reactions and infections to find attractive and specific therapeutic interventions for urticarial symptomatology.

Acute Disease↗
PubMed2004

Rapid identification and differentiation of fungal DNA in dermatological specimens by LightCycler PCR.

The aim was to develop a LightCycler PCR method for the rapid detection and differentiation of fungal DNA in dermatological specimens such as skin scales and skin swabs. LightCycler PCR assays were established for seven primer sets specific for fungal DNA. For each primer set LightCycler melting points were defined by amplification of DNA from 21 fungi and sensitivity was determined by amplification of serial dilutions of fungal DNA. A protocol was established that allows detection and differentiation of mould and yeast DNA with one highly sensitive PCR reaction by assessment of LightCycler melting points. Two subsequent LightCycler PCR reactions and one RFLP reaction allowed the differentiation of dermatophytes and non-dermatophyte moulds and the subclassification of yeasts. Analysis of clinical samples from 38 patients with fungal skin diseases provided conclusive new diagnostic information in 9/38 cases (23.7 %) by this PCR protocol that was not equally provided by direct microscopy and mycological culture. Thus the LightCycler PCR protocol established here represents a rapid diagnostic tool that aids in the diagnosis of fungal skin disease in a substantial number of patients.

DNA, Fungal↗
PubMed2004

Human monocyte-derived dendritic cells are chemoattracted to C3a after up-regulation of the C3a receptor with interferons.

The anaphylatoxin C3a is an important inflammatory mediator in the innate and adaptive immune systems. Recent reports in various animal models have fostered the role of C3a in mediating allergic reactions such as pulmonary allergies. However, data in humans are limited and the cellular targets for C3a are not fully understood. We sought to explore human dendritic cells as a new target for C3a, because C3a receptor (C3aR) expression has been described on myeloid cells, and dendritic cells are likely make contact with C3a at sites of inflammatory reactions. In this study, we demonstrated the expression of the C3aR on human monocyte-derived dendritic cells (MoDC) and its up-regulation by interferon (IFN)-alpha, IFN-gamma and prostaglandin E2 (PGE2). The strongest up-regulation was yielded by the combination of IFN-alpha+ IFN-gamma. Tumour necrosis factor-alpha (TNF-alpha) down-regulated the C3aR. After up-regulation of the C3aR by IFN-alpha+ IFN-gamma, C3a significantly up-regulated the surface expression of CD54, CD83 and CD86, but not of CD40, CD80 or human leucocyte antigen (HLA)-DR. C3a had no effect on the production of interleukin (IL)-10 or IL-12p70, or on the capacity of MoDC to stimulate autologous T-cell proliferation. However, C3a had a direct migratory effect on MoDC, as indicated by the induction of F-actin polymerization and migration in Boyden chamber experiments, which was pronounced after up-regulation of the C3aR with IFN-alpha+ IFN-gamma. Therefore, dendritic cells represent another group of target cells that might be recruited by C3a to areas of inflammation, in particular under conditions where IFNs are increased in the surrounding environment.

Cell Division↗
PubMed2004

Influence of pimecrolimus cream 1% on different morphological signs of eczema in infants with atopic dermatitis.

BACKGROUND: In the published studies on the efficacy of the topical immunomodulator pimecrolimus, different eczema scores were used, and the impact on morphological key signs of eczema was not analysed. OBJECTIVE: To compare the influence of pimecrolimus cream 1% on different standard eczema scores in infants with atopic dermatitis and to analyse the impact of treatment on the individual morphological key signs of eczema. METHODS: Pimecrolimus cream 1% (n = 129) or double-blind vehicle control (n = 66) was administered for 4 weeks. The Eczema Area and Severity Index (EASI), Investigators' Global Assessment (IGA) and Scoring Atopic Dermatitis Index (SCORAD) were determined and were correlated with each other. RESULTS: Following treatment with pimecrolimus, the EASI, IGA and SCORAD were significantly reduced on day 29 as compared with the vehicle group (p < 0.001, p < 0.001, p = 0.002, respectively). There was a close correlation between EASI, IGA and SCORAD. The single parameters of the EASI were already significantly decreased by day 4 in the pimecrolimus group as compared to vehicle (each p < 0.001). CONCLUSION: Treatment with pimecrolimus 1% cream leads to a rapid improvement of all morphological signs of eczema. The close correlation of different scores was shown for the first time.

Administration, Topical↗
PubMed2003

Human dendritic cells express the IL-18R and are chemoattracted to IL-18.

IL-18 is secreted by a variety of cells such as epithelial cells, macrophages, and dendritic cells (DC), in particular, in areas of chronic inflammation. The effects of IL-18 are complex and not fully understood thus far. We sought to explore human DC as a new target for IL-18, since IL-18R expression has been described on myeloid cells such as macrophages and DC are likely to get in contact with IL-18 at sites of inflammatory reactions. We demonstrate the expression of the IL-18R on human DC in peripheral blood and epidermis, as well as monocyte-derived dendritic cells (MoDC). On MoDC, IL-18R expression is up-regulated by IFN-gamma. IL-18 strongly up-regulated CD54 on MoDC, whereas the effect on MHC class II, CD83, and CD86 was only moderate and the expression of CD40 and CD80 was not affected. MoDC primed with IL-18 did not increase their capacity to stimulate the proliferation or IFN-gamma production of autologous T cells. However, IL-18 had a direct migratory effect on MoDC as indicated by induction of filamentous actin polymerization and migration in Boyden chamber experiments. In epidermal DC, IL-18 was also able to induce filamentous actin polymerization. Therefore, IL-18 might represent a novel mechanism to recruit DC to areas of inflammation, in particular under Th1 cytokine conditions where IFN-gamma is increased such as psoriasis or inflammatory bowel diseases.

Actins↗
PubMed2003

Up-regulation of C5a receptor expression and function on human monocyte derived dendritic cells by prostaglandin E2.

The expression of the C5a-receptor (C5aR) on dendritic cells, its regulation and function have not been well established thus far. We show that the C5aR is expressed on human monocyte-derived dendritic cells (DC) and can be down-regulated by maturation stimuli such as tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS) or CD40L and by the T helper 1-cytokine interferon-gamma (INF-gamma). Prostaglandin E2 (PGE2), a proinflammatory mediator supporting dendritic cell activation and necessary for adequate DC migration, leads to the up-regulation of C5aR expression when incubated alone and prevents down-regulation when given in combination with TNF-alpha or LPS. Stimulation of C5aR on DC triggered F-actin polymerization, indicating the chemotactic potential of DC elicited by C5a. C5a induced F-actin polymerization was increased when C5aR was up-regulated by PGE2. Stimulation of DC with C5a resulted in interleukin-10 production which was significantly increased after C5aR up-regulation with TNF-alpha and PGE2. Therefore, up-regulation of the C5aR on human DC alters their chemotactic and immunologic response to C5a.

Actins↗
PubMed2002

Suppression of IL-12 production by soluble CD40 ligand: evidence for involvement of the p44/42 mitogen-activated protein kinase pathway.

IL-12 is a key cytokine in skewing immune responses toward Th1-like reactions. Human monocytes/macrophages produce high amounts of bioactive IL-12 when a priming signal (IFN-gamma or GM-CSF) precedes a second signal (e.g., LPS). We and others have previously shown that preincubation with LPS before this stimulation procedure can efficiently and selectively suppress the production of IL-12 by human monocytes. In this study, we show that an almost complete suppression of IL-12 production can also be observed after preincubation of monocytes with costimulatory cell surface molecules that bind to members of the TNFR superfamily (CD40 ligand, TNF-related activation-induced cytokine (TRANCE)). The suppression of IL-12 was observable on the mRNA and protein levels and was not due to endogenous production of known IL-12 antagonists (i.e., IL-10, IL-4, and PGE(2)), to an increased number of cells undergoing apoptosis, nor to down-regulation of the IFN-gamma or CD40 receptor. Cell surface expression of the costimulatory molecules CD80 and CD86 was not reduced by the preincubation procedure, and only a moderate reduction of IL-6 production was observed. Several studies have identified signal transduction pathways that are activated by CD40 signaling, including activation of mitogen-activated protein kinases. The presence of the extracellular signal-related kinase-specific mitogen-activated protein kinase kinase 1/2-specific inhibitors PD98059 and U0126 abrogated suppression induced by sCD40 ligand or other second signals. This indicates that activation of extracellular signal-regulated kinase 1/2 contributes to the underlying mechanism of IL-12 suppression. This mechanism may be relevant in other inflammatory responses and may help to develop therapeutic strategies in Th1-mediated diseases.

Apoptosis↗
PubMed2002

Absence of HHV-8 DNA in hobnail hemangiomas.

BACKGROUND: Hobnail hemangioma (HH) is a rare subtype of hemangioma that shares the morphological feature of hobnail endothelia with retiform hemangioendothelioma (RHE) and has to be considered in the differential diagnosis of Kaposi sarcoma. Since DNA of the human herpesvirus type 8 (HHV-8) has been detected in more than 90% of Karposi sarcomas and could recently be demonstrated in RHE, we sought to detect HHV-8 DNA in HH. METHODS AND RESULTS: DNA from 12 HH was extracted and subjected to polymerase chain reaction analysis for HHV-8 DNA using two independent protocols with a single set of primers and a nested PCR approach, respectively. PCR amplification was performed using the LightCycler as well as using a thermocycler. HHV-8 DNA could not be detected in HH, although each sample contained DNA adaequately preserved for PCR reactions, as determined by amplification of the beta actin gene. CONCLUSIONS: HHV-8 appears to play no rule in the pathogenesis of HH. Absence of HHV-8 DNA in HH might be important in the differential diagnosis to other vascular tumours, in particular Kaposi sarcoma.

DNA Primers↗
PubMed2002

Staphylococcal exotoxins exert proinflammatory effects through inhibition of eosinophil apoptosis, increased surface antigen expression (CD11b, CD45, CD54, and CD69), and enhanced cytokine-activated oxidative burst, thereby triggering allergic inflammatory reactions.

BACKGROUND: Staphylococcus aureus colonization of the skin represents a potent trigger factor of atopic dermatitis. Our previous studies demonstrated that in atopic dermatitis eosinophil apoptosis is significantly delayed. OBJECTIVE: We sought to investigate the effect of staphylococcal exotoxins (SETs) on eosinophil apoptosis and functional activities. METHODS: Apoptotic eosinophils were investigated by determining their hypodiploid DNA peak. Eosinophil surface-antigen expression and intracellular production of hydrogen peroxide were assessed by means of flow cytometric analysis and respiratory burst by lucigenin-dependent chemiluminescence. RESULTS: The SETs SEA, SEB, SEC, and toxic shock syndrome toxin 1 significantly inhibited eosinophil apoptosis in a manner comparable with that of high concentrations of IL-3. The LPS inhibitor polymyxin B was found to significantly inhibit LPS-mediated, but not SET-mediated, inhibition of apoptosis. Neither SETs nor LPS was able to modulate eosinophil surface expression of CD9, CD11a, CD16, CD40, CD44, or CD63. However, 24- and 48-hour incubation with all SETs, but not with LPS, significantly upregulated expression of CD11b and CD45 in a manner similar to that of IL-3, whereas dexamethasone induced a downregulation. Moreover, all SETs resulted in a significant upregulation of CD54 after 24 hours but not after 48 hours. Interestingly, CD69 was upregulated by means of IL-3 and SEB only. Neither direct stimulation of eosinophils nor 24-hour incubation with SETs or stimulation with SETs after a 24-hour prestimulation with IL-3, IL-5, or GM-CSF resulted in a significant extracellular production of reactive oxygen species or in a significant production of intracellular hydrogen peroxide. However, SEB and toxic shock syndrome toxin 1 were able to enhance cytokine-induced respiratory burst. CONCLUSION: Taken together, our data demonstrate that SETs may modulate the course of the allergic inflammatory response through modulation of potent eosinophil effector functions. This may be of particular importance in atopic dermatitis, in which the skin is regularly colonized with SET-producing S aureus.

Antigens, CD↗
PubMed2002

Expression and function of histamine receptors 1 and 2 on human monocyte-derived dendritic cells.

BACKGROUND: Histamine is a well-known mediator of inflammatory and allergic reactions and has immunomodulatory capacities. There is increasing evidence that dendritic cells as professional antigen-presenting cells play a major role in the development of allergic reactions. However, a possible link between histamine and dendritic cells has not been investigated thus far. OBJECTIVE: We investigated the effect of histamine on human monocyte-derived dendritic cells (MoDCs). METHODS: Expression of histamine H1 and H2 receptors (H1R and H2R) on MoDCs was assessed by means of RT-PCR and flow cytometry. Functional exploration of these receptors was performed by monitoring the increase of intracellular calcium levels (H1R), cyclic adenosine monophosphate formation (H2R), F-actin polymerization, and IL-12p70 production. RESULTS: MoDCs express both H1R and H2R. Stimulation of dendritic cells with histamine resulted in F-actin polymerization and cyclic adenosine monophosphate production through H2R. Influx of calcium could not be detected after stimulation of dendritic cells with histamine under conditions in which histamine induced calcium influx in monocytes. Histamine and H1R and H2R agonists downregulated IL-12p70 production of prestimulated MoDCs. CONCLUSION: MoDCs express histamine H1 and H2 receptors. Our results indicate chemotactic (F-actin polymerization) and immunomodulatory (inhibition of IL-12p70 production) effects of histamine on MoDCs. Therefore histamine might represent a link between immediate-type hypersensitivity reactions and cellular inflammation in allergic disease (eg, in atopic dermatitis).

Actins↗
PubMed2002

Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid anti-inflammatory drug.

BACKGROUND: Pimecrolimus cream 1% (Elidel, SDZ ASM 981), a nonsteroid selective inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). In this study we compared early intervention with pimecrolimus cream with treatment with a vehicle control. OBJECTIVE: The purpose of this investigation was to assess whether early treatment in infants of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares. METHODS: In this 1-year, double-blind controlled study, 251 infants aged 3 to 23 months with AD were randomized 4:1 to a pimecrolimus-based regimen (n = 204) or a conventional treatment regimen (n = 47). Both groups used emollients for dry skin. Early AD signs and symptoms were treated either with pimecrolimus cream to prevent flares or, in the control group, with vehicle. Vehicle was used to maintain blinding conditions. In the event of flares, moderately potent corticosteroid was permitted in both groups. The primary efficacy end point was the incidence of flares at 6 months. RESULTS: Pimecrolimus significantly reduced the incidence of flares compared with control treatment (P <.001), with 67.6% versus 30.4% of patients completing 6 months with no flare and 56.9% versus 28.3% completing 12 months with no flare. Overall corticosteroid use was substantially lower in the pimecrolimus group: 63.7% versus 34.8% of patients did not use corticosteroids at all during the study. Pimecrolimus was also more effective than control treatment in the long-term control of pruritus and the signs of AD. There were no clinically significant differences in incidence of adverse events between the 2 treatment groups. CONCLUSIONS: Treatment with pimecrolimus of early signs and symptoms significantly modified the disease course in infants by reducing the incidence of flares and improving overall control of AD. Pimecrolimus was safe and well tolerated.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Helicobacter pylori infection in skin diseases: a critical appraisal.

More than 50% of the human population have long-term Helicobacter pylori infection, causing, in some cases, severe diseases such as peptic ulcers and stomach cancer. In the last few years several extra-gastrointestinal disorders have been associated with H. pylori infection. This review summarized the current medical literature, identified through hand searching and MEDLINE research, including our own studies, with regard to H. pylori and skin diseases. From the literature it can be seen that the role of H. pylori in skin diseases is still a controversial subject. Randomized controlled trials with adequate masking and sample sizes are still lacking. The best evidence comes from studies investigating chronic urticaria in which chronic urticaria disappeared in many patients with H. pylori infection after careful eradication of the H. pylori. Moreover, there are promising recent reports of beneficial H. pylori eradication in Behçet's disease, pruritus cutaneus, prurigo chronica, prurigo nodularis and in some patients with lichen planus, but not in rosacea or psoriasis. Before any conclusions with respect to other skin diseases such as atopic dermatitis, Schoenlein-Henoch Purpura, Sweet's syndrome, Sjögren syndrome or systemic sclerosis may be drawn, additional randomized, double-blinded and placebo-controlled studies including adequate diagnostic schedules, sufficient eradication treatment protocols, confirmation of eradication and adequate control groups are needed. The cutaneous pathology of H. pylori is far from being clear, but it is speculated that the systemic effects may involve increased mucosal permeability to alimentary antigens, immunomodulation, an autoimmune mechanism or the impairment of vascular integrity.

Amoxicillin↗