Large Variability of Frequency and Type of Physical Therapy in Patients in the German Network for Systemic Sclerosis.

OBJECTIVE: To determine the type and frequency of physical therapy (PT) prescribed by physicians for patients in the registry of the German Network for Systemic Sclerosis. METHODS: The data for 4,252 patients were analyzed using descriptive statistics, chi-square tests, and odds ratios (ORs). RESULTS: Overall, 37.4% of patients (1,590 of 4,252) received PT at the end of a yearly follow-up. The most frequently used type of PT was lymphatic drainage (n = 1,061, 36.8%), followed by exercise therapy (n = 1,047, 36.3%) and heat therapy (n = 689, 23.9%). More than three-fourths of treated patients (82%) received 1 or 2 different forms of PT simultaneously. The prescription of PT was associated with the extent of skin fibrosis as measured by the modified Rodnan skin thickness score (<10 [41.8% of patients], 11-20 [55.8% of patients], and >21 [63.9% of patients]; P < 0.001). Patients with musculoskeletal involvement (e.g., arthritis, muscle weakness, joint contractures, tendon friction rubs) had a higher chance of receiving PT than patients without these symptoms, with corresponding ORs ranging from 1.96 (95% confidence interval [95% CI] 1.69-2.28) for joint contractures to 3.83 (95% CI 2.89-5.08) for arthritis. When comparing the type of PT prescription across the initial and all follow-up visits from 2003 to 2017, significant alterations with a decreasing frequency of patients receiving PT could be observed (P = 0.001). CONCLUSION: To our knowledge, this is the first study reporting the use of PT in patients with systemic sclerosis (SSc) in a large cohort. Although SSc is characterized by considerable disability and restriction of motion, <40% of patients received PT.

Randomized controlled trials define shape of dose response for Pollinex Quattro Birch allergoid immunotherapy.

BACKGROUND: The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX® Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed 2 phase II studies to determine its optimal cumulative dose. METHODS: The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3-4 weeks after completing treatment, to quantify the reduction in Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modeling analysis was used to test for the dose response, shape of the curve and estimation of the median effective dose (ED50 ), a measure of potency. RESULTS: Statistically significant dose responses (P < .01 & .001) were seen, respectively. The highest cumulative dose in PQBirch204 (27 300 standardized units [SU]) approached a plateau. Potency of the PQBirch was demonstrated by an ED50 2723 SU, just over half the current dose. Prevalence of treatment-emergent adverse events was similar for active doses, most being short-lived and mild. Compliance was over 85% in all groups. CONCLUSION: Increasing the cumulative dose of PQBirch 5.5-fold from 5100 to 27 300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase in efficacy of 50%, without compromising safety. The cumulative dose response was confirmed to be curvilinear in shape.

Dose-response relationship of a new Timothy grass pollen allergoid in comparison with a 6-grass pollen allergoid.

BACKGROUND: Subcutaneous allergen immunotherapy with grass pollen allergoids has been proven to be effective and safe in the treatment of patients with allergic rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae species, it has been suggested that grass pollen extracts could be prepared from a single species, rather than from a multiple species mixture. OBJECTIVE: To find the optimal dose of a Phleum pratense (P. pratense) allergoid preparation and compare its efficacy and safety to a 6-grass pollen allergoid preparation. METHODS: In this double-blind, placebo-controlled study (EudraCT: 2011-000674-58), three doses of P. pratense allergoid (1800 therapeutic units (TU), standard-dose 6000 TU and 18 000 TU) were compared with placebo and the marketed 6-grass pollen allergoid (6000 TU). In a pre-seasonal dosing regimen, 102 patients were randomized to five treatment groups and received nine subcutaneous injections. The primary efficacy endpoint was the change in weal size (late-phase reaction [LPR]) in response to the intracutaneous testing (ICT) before and after treatment, comparing the active allergoids to placebo. Secondary outcomes were the change in Total Nasal Symptom Score (TNSS) assessed in the allergen exposure chamber (AEC), the changes in P. pratense-serum-specific IgG4 and the incidence of adverse events (AEs). RESULTS: All three doses of the P. pratense and the 6-grass pollen allergoid preparations were significantly superior to placebo for the primary outcome, whereas there were no significant differences in the change in TNSS. Compared to the standard-dose, the high-dose of P. pratense did not produce any additional significant benefit, but showed a slight increase in AEs. Yet this increase in AEs was lower than for the 6-grass pollen preparation. CONCLUSIONS & CLINICAL RELEVANCE: The standard-dose of the new P. pratense allergoid was comparable to the marketed 6-grass pollen preparation at equal dose for the parameters measured.

[Placebo response - Mechanisms and clinical applications]. / Placeboreaktion ­ Mechanismen und klinische Anwendungen.

Research on placebo responses has made major progress in recent years. Placebo responses are psychobiological events, which are created by the entire therapeutic context. They can appear at any time, not only in experimental and clinical settings. Several studies on analgesia-related placebo research showed that patients have higher placebo responses in comparison to healthy participants, which may also last longer. Expectations play a key role in placebo analgesia. They can be induced via three central psychological mechanisms: 1) expectation induced via instructions, 2) expectation induced via classical conditioning and 3) expectation induced via social learning. These mechanisms are controlled by neurobiological structures and modulate pain perception resulting in pain relief by positive expectations and increased pain by negative expectations, the so-called nocebo effect. There is an ongoing discussion that these psychological mechanisms may also play a central role in inducing and maintaining itch-reducing placebo responses. The current state of research suggests that placebo responses could be used in clinical contexts and should not be viewed as being in competition with medications but as an additive increase in efficacy of a pharmacological substance through specifically induced placebo responses. This targeted use is also possible within ethical guidelines. Important prerequisites are that the research results can be transferred from healthy participants to patients and that the placebo responses are reproducible.

Characterization of oral immune cells in birch pollen-allergic patients: impact of the oral allergy syndrome and sublingual allergen immunotherapy on antigen-presenting cells.

BACKGROUND: A detailed characterization of human oral immune cells is needed to better understand local mechanisms associated with allergen capture following oral exposure. METHODS: Oral immune cells were characterized by immunohistology and immunofluorescence in biopsies obtained from three healthy individuals and 23 birch pollen-allergic patients with/without oral allergy syndrome (OAS), at baseline and after 5 months of sublingual allergen immunotherapy (AIT). RESULTS: Similar cell subsets (i.e., dendritic cells, mast cells, and T lymphocytes) were detected in oral tissues from healthy and birch pollen-allergic individuals. CD207+ Langerhans cells (LCs) and CD11c+ myeloid dendritic cells (DCs) were found in both the epithelium and the papillary layer of the Lamina propria (LP), whereas CD68+ macrophages, CD117+ mast cells, and CD4+ /CD8+ T cells were rather located in both the papillary and reticular layers of the LP. Patterns of oral immune cells were identical in patients with/without OAS, except lower numbers of CD207+ LCs found in oral tissues from patients with OAS, when compared to OAS- patients (P < 0.05). A 5-month sublingual AIT had a limited impact on oral immune cells, with only a significant increase in IgE+ cells in patients from the active group. Colocalization experiments confirmed that such IgE-expressing cells mostly encompass CD68+ macrophages located in the LP, and to a lesser extent CD207+ LCs in the epithelium. CONCLUSION: Two cell subsets contribute to antigen/allergen uptake in human oral tissues, including (i) CD207+ LCs possibly involved in the physiopathology of OAS and (ii) CD68+ macrophages likely critical in allergen capture via IgE-facilitated mechanisms during sublingual AIT.

Association of vitamin D receptor gene polymorphisms with severe atopic dermatitis in adults.

BACKGROUND: Vitamin D mediates immunomodulatory functions, and beneficial functions in allergic diseases have been suggested. Vitamin D receptor gene (VDR) polymorphisms are known but have not been studied in patients with atopic dermatitis (AD). OBJECTIVES: To investigate the frequency of four common VDR gene polymorphisms in patients with AD, and their potential functional relevance. METHODS: In this case-control study, 265 patients with AD [n=142 severe AD, Scoring AD index (SCORAD) > 40; n=123 moderate AD, SCORAD 15-40] and 265 healthy controls were genotyped for four common VDR gene polymorphisms by restriction fragment length polymorphism analysis. The VDR haplotype sequences were analysed in silico. Baseline and activation-induced gene expression of VDR and the vitamin D metabolizing enzyme CYP24A1 were analysed in monocytes of homozygous VDR haplotype carriers by quantitative reverse transcription-polymerase chain reaction. RESULTS: In patients with severe AD, the VDR BsmI (rs1544410) G allele, ApaI (rs7975232) C allele and TaqI (rs731236) T alleles were over-represented compared with healthy controls. These single nucleotide polymorphisms (SNP) were tightly linked, and the VDR haplotype GCT was correlated with severe AD and complementary AAC with protection from AD. The VDR haplotype GCT region is evolutionarily conserved. The VDR FokI (rs2228570) SNP was not associated with AD. Baseline VDR expression in monocytes and short-term activation were haplotype independent. CONCLUSION: A specific VDR haplotype is more frequent in patients with severe AD. These data indicate that VDR contributes to the control of AD, e.g. by regulation of the epidermal barrier function and/or local immune response.

Sustained clinical efficacy of sublingual immunotherapy with a high-dose grass pollen extract.

BACKGROUND: Sublingual immunotherapy (SLIT) with a high-dose 6-grass pollen SingleDose preparation was shown to be effective and safe in a 2-year randomized, double-blind, placebo-controlled trial. OBJECTIVE: We evaluated the effect of the third year of SLIT in comparison to the second year. METHODS: 46 grass pollen-allergic patients who had received active treatment for 3 consecutive years were included in the safety set. Diary data from 39 subjects were evaluated to calculate symptom and medication scores as well as 'well days'. RESULTS: Symptoms and medication intake further decreased in the third year of SLIT during the grass pollen season in comparison to the previous years and the number of 'well days' increased accordingly. No serious adverse events occurred during the three years of SLIT. CONCLUSION: The third year of SLIT with the high-dose 6-grass pollen preparation results in sustained and even further increased clinical efficacy.

Efficient tetanus toxoid immunization on vitamin D supplementation.

BACKGROUND/OBJECTIVES: Vitamin D mediates immunomodulatory functions, and its deficiency has been associated with an increased prevalence of immunological diseases. The supplementation of vitamin D might be therapeutically beneficial, for example, in lupus erythematosus patients. However, its affect on established recall immune responses is undefined. SUBJECTS/METHODS: In all, 32 individuals were randomized in a placebo controlled, double-blind setting, and received vitamin D (daily 2000 IU) for 10 weeks followed by tetanus toxoid (TT) booster immunization. RESULTS: During vitamin D supplementation the median 25-hydroxyvitamin D serum concentration increased to 80.3 nM, which as expected decreased in the placebo group to 29.1 nM during the ultraviolet-deprived winter months. The TT-specific immunoglobulin G (IgG) boost efficiency was marginal higher in the vitamin D group (P = 0.04). The increase of the 25-hydroxyvitamin D levels correlated with the increase of TT-IgG serum concentrations. The induction of specific serum IgA and specific antibody secreting cells was comparable between both groups. Accordingly, the TT-specific and polyclonally triggered T-cell cytokine profiles were stable as well. CONCLUSIONS: Vitamin D supplementation was successful and booster immunization induced efficiently specific antibodies titers.

Vitamin D deficiency in patients with cutaneous lupus erythematosus is prevalent throughout the year.

BACKGROUND: Vitamin D mediates immunomodulatory functions and its deficiency has been associated with an increased prevalence of immunological diseases including systemic lupus erythematosus (SLE). Chronic discoid or subacute cutaneous lupus erythematosus (CLE) are ultraviolet (UV)-triggered skin diseases. As vitamin D is mostly UV-derived and not from nutrition, its deficiency is frequent especially during the UV-deprived winter months. OBJECTIVE: To compare the vitamin D status of patients with CLE with patients with type I allergy and healthy individuals during the summer or winter months. METHODS: The vitamin D status of patients with CLE (n = 41) was compared with patients with type I allergy (n = 24), healthy individuals (n = 25) and a reference pool (n = 1951) by means of concentrations of circulating storage metabolite 25-hydroxyvitamin D in the summer and winter. RESULTS: Serum 25-hydroxyvitamin D concentrations were lower during the winter in the reference population, and type I allergic and healthy individuals (29.2­35.5 nmol L)1) compared with the summer months (56.3­89.8 nmol L)1) and paralleled by the prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D< 50 nmol L)1; winter: 70.8­73.4%, summer: 34.9­39.4%). In contrast, vitamin D deficiency in patients with CLE was prevalent throughout the year (summer: 85.7%,winter: 97.1%). In patients with CLE with concomitant prednisolone treatment, the 25-hydroxyvitamin D serum levels were comparable with (mean daily intake 877 IU) or without vitamin D supplementation during summer or winter (P = 0.75 and P = 0.14, respectively). CONCLUSIONS: Our data identify vitamin D deficiency in patients with CLE throughout the year and indicate that monitoring and correcting the vitamin D status should be considered to prevent bone demineralization and fractures and to modulate beneficially immunological dysfunction.

Implementation of pre-seasonal sublingual immunotherapy with a five-grass pollen tablet during optimal dosage assessment.

BACKGROUND: The optimal dose (300IR) of a five-grass pollen sublingual immunotherapy tablet in terms of efficacy was previously demonstrated from the first pollen season. OBJECTIVE: Here, we aim to confirm whether this dose remained optimal during the peak of the pollen season by assessing the efficacy and quality of life data. METHODS: A total of 628 subjects with grass pollen rhinoconjunctivitis were randomized in a double-blind, placebo-controlled, multi-centre, pan-European trial. Subjects received once-daily tablets (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before and throughout the 2005 grass pollen season. The pollen season was defined as the first day of 3 consecutive days with a grass pollen count above 30 grains/m(3) of air, recorded using Hirst-type volumetric pollen traps, to the last day before 3 consecutive days with a pollen count below 30 grains/m(3). RESULTS: The grass pollen season lasted an average of 30 days, with a peak of 12 days. The mean treatment duration before the grass pollen season was similar in the four treatment groups (121.4+/-31.1 to 128.6+/-15.4 days in the safety population). Both the 300IR and 500IR groups had highly significant improvements in Rhinoconjunctivitis Total Symptom Score (RTSS) vs. placebo at the peak pollen season (P=0.0005 and 0.0014, respectively), which agreed with improvements in RTSS in the primary evaluations. The average RTSS scores were slightly elevated during the peak pollen season in all treatment groups. The overall Rhinoconjunctivitis Quality of Life Questionnaire score confirmed the optimal dosage 300IR at peak (P<0.0001) and at the end (P< or =0.0031) of the pollen season. All doses were well tolerated. CONCLUSION: At the peak pollen season, the efficacy and quality of life data for both 300IR and 500IR groups was significantly improved vs. the placebo group. These results confirm the conclusions of the primary evaluations and validate the use of 300IR tablets for clinical practice.

Impact of native, heat-processed and encapsulated hazelnuts on the allergic response in hazelnut-allergic patients.

BACKGROUND: Pollen-associated food allergy is common. However, systemic reactions or even life-threatening anaphylaxis are rare. OBJECTIVE: The aim of this study was to investigate the clinical impact of native, heat-processed and encapsulated hazelnuts (HN) in patients with proven HN allergy. METHODS: One hundred and thirty-two patients with a positive history of HN allergy were recruited. Sensitization was confirmed by a skin prick test (SPT) and sIgE against HN. After an HN-free diet, double-blind placebo-controlled challenges were performed with increasing amounts of native and roasted HN. A subset of patients were given HN capsules to circumvent the oral mucosa. Basophil activation was measured by flow cytometry before and after provocation but also ex vivo using native and roasted HN extracts. RESULTS: Three groups of HN-allergic patients were identified depending on their clinical reaction pattern. The dosages by which allergic reactions were elicitated varied for native HN from 0.01 to 2.0 g, with a median of 0.1 g, for roasted HN from 0.01 to 10.0 g, with a median of 0.23 g, and for encapsulated HN from 0.1 to 3.0 g, with a median of 0.3 g. Accordingly, the SPT was more frequently positive and resulted in greater weal reactions if native HN was used. This finding was confirmed by ex vivo basophil activation showing that significantly higher allergen extract concentrations (roasted>native) were necessary to induce 50% basophil activation. CONCLUSION: Our data show that heat processing of HN reduces its allergenicity. SPT but also the basophil activation test can be used to determine the reactivity of an allergen extract.

Agreement of efficacy assessments for five-grass pollen sublingual tablet immunotherapy.

BACKGROUND: The optimal dose of five-grass pollen sublingual tablet immunotherapy (SLIT) was established recently by the primary criteria Rhinoconjunctivitis Total Symptom Score (RTSS) from the first treatment season. Secondary and exploratory criteria, such as RTSS at peak pollen season, exploratory combined symptom and rescue medication use score, quality of life and immunological markers are calculated and described in this analysis. METHODS: Six hundred and twenty-eight patients with grass pollen rhinoconjunctivitis (> or =2 years duration) were randomized in a double-blind, placebo-controlled trial conducted in Europe. Patients received once-daily SLIT (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before grass pollen season and throughout the 2005 season. Patients were instructed to take rescue medication only if symptoms were severe and record symptom severity on using the RTSS. RESULTS: Both 300IR and 500IR doses significantly reduced mean RTSS at pollen peak (P = 0.0005 and P = 0.0014, respectively) and the exploratory combined score (P = 0.0001 and P = 0.0026, respectively) compared with placebo. Compared with patients in the placebo group, those who were taking the 300IR and 500IR doses reported significantly improved quality of life using the mean Rhinoconjunctivitis Quality of Life Questionnaire scores during the peak of the pollen season (P < 0.0001) and at the end of the pollen season (P = 0.0031 and P < or = 0.0001, respectively). Specific immunoglobulin G4 increased significantly depending on the SLIT dose (P < 0.0001). CONCLUSIONS: All secondary efficacy criteria, including efficacy at pollen peak, combined score, quality of life and immunological changes, indicate that 300IR tablets represent the optimal dose and suggest it is appropriate for use in clinical practice.

Docosahexaenoic acid (DHA) supplementation in atopic eczema: a randomized, double-blind, controlled trial.

BACKGROUND: The increasing prevalence of atopic eczema has been linked to the alteration of the Western diet, namely the reduced consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFA) and an increased omega-6 (n-6) PUFA intake. OBJECTIVES: The aim of the pilot study was to determine the efficacy of dietary n-3 PUFA docosahexaenoic acid (DHA) in patients with atopic eczema. METHODS: Fifty-three patients suffering from atopic eczema aged 18-40 years were recruited into this randomized, double-blind, controlled trial and received either DHA 5.4 g daily (n = 21) or an isoenergetic control of saturated fatty acids (n = 23) for 8 weeks. At weeks 0, 4, 8 and 20 the clinical outcome was assessed by the SCORAD (severity scoring of atopic dermatitis) index. IgE production and activation of peripheral blood mononuclear cells (PBMC) were analysed. Plasma fatty acids were measured by gas chromatography. RESULTS: DHA, but not the control treatment, resulted in a significant clinical improvement of atopic eczema in terms of a decreased SCORAD [DHA: baseline 37.0 (17.9-48.0), week 8 28.5 (17.6-51.0); control: baseline 35.4 (17.2-63.0), week 8 33.4 (10.7-56.2)]. A significant reduction of anti-CD40/interleukin 4-mediated IgE synthesis of PBMC was detected in the DHA group only. Supplementation led to a modulated activation status of PBMC in both groups. The DHA group showed an increase of plasma n-3 PUFA and a decrease in the n-6/n-3 PUFA ratio. CONCLUSIONS: Our data suggest that dietary DHA could be bioactive and might have a beneficial impact on the outcome of atopic eczema, but our results need to be confirmed in a larger study.

Penetration of pollen proteins into the skin.

Atopic dermatitis is a chronic remittent skin disease. In the extrinsic form of atopic dermatitis, type IgE-mediated reactions play an important pathophysiological role. The aim of the present study was to examine whether type I allergens can penetrate into the skin. Therefore, pollen proteins were labeled with fluorescein isothiocyanate (FITC), and their penetration profile was studied qualitatively. Solutions of FITC-labeled pollen proteins were applied in vitro on porcine skin and in vivo on human skin. In vitro, the FITC-labeled proteins were observed within the complete stratum corneum (SC) and inside the hair follicles even 15 min after application. They were also distributed inside the dermis around the hair follicles. In vivo, a similar pattern of distribution within the SC and the hair follicles was observed. These results indicate penetration via the SC lipid layers and a faster penetration via the hair follicles. The FITC-labeled proteins entered the dermis via the follicular pathway. Therefore, the follicular penetration should be considered in the development of skin protection strategies. To evaluate such strategies, the developed method can be used, and further studies in atopic dermatitis patients are necessary to determine whether the penetration of type I allergens is increased.

Neutrophil respiratory burst is decreased in scleroderma and normalized by near-infrared mediated hyperthermia.

BACKGROUND: The production of reactive oxygen species (ROS) by fibroblasts has been suggested to contribute to scleroderma pathogenesis. Infrared-mediated hyperthermia has recently been shown to be of benefit in scleroderma. AIM: As the contribution of neutrophils and monocytes to ROS formation in scleroderma is unknown, we studied respiratory burst in these cell types. We also aimed to test the hypothesis that near-infrared (IRA) treatment may effect burst activity. METHODS: We determined respiratory burst in patients with scleroderma (n = 22) and age- and sex-matched controls (n = 20) at baseline, and after high-level stimulation by phorbolmyristyl acetate (PMA) and low-level stimulation by non-opsonized zymosan. Respiratory burst was also assessed before and after a series of infrared-mediated hyperthermia treatments. RESULTS: Unexpectedly, we observed no increase but instead a slight but statistically significant reduction in baseline and zymosan-stimulated respiratory burst in scleroderma neutrophils (P < 0.001) and monocytes (P < 0.005). This decrease in burst activity was nonspecific, as it was also observed in patients with another active inflammatory disease, psoriasis. IRA treatment induced a cell-type-specific normalization of respiratory burst only in neutrophils, but not in monocytes. Intriguingly, neutrophil-specific normalization of ROS formation persisted for 6 weeks after the end of IRA treatment, in concordance with the previously reported clinical responses to this therapy. CONCLUSION: Neutrophils and monocytes do not exhibit cell-autonomous overproduction of ROS in scleroderma, thereby implicating fibroblasts as main source for clinically relevant ROS accumulation. Furthermore, repeated mild infrared-mediated hyperthermia exerts a lasting cell-type-specific effect on neutrophils.

Efficacy and tolerability of high dose sublingual immunotherapy in patients with rhinoconjunctivitis.

In a multi-centre, randomized, double-blind, placebo-controlled clinical trial over 3 years high dose sublingual specific immunotherapy with an extract of a 6-grass-pollen mixture showed a highly significant and clinically relevant improvement in patients with grass pollen rhinitis/-conjunctivitis with or without asthma and an increase in allergen specific antibodies (IgG1, IgG4) indicating immunological efficacy. A difference of 46% in mean symptom medication score between active and placebo group was seen. The treatment with the sublingual solution was well tolerated. High dose sublingual immunotherapy can therefore be considered as an efficient therapeutic option in the management of IgE-mediated allergic airway diseases.

Allergen-mediated modulation of CD23 expression is interferon-gamma and interleukin-10 dependent in allergic and non-allergic individuals.

BACKGROUND: CD23 plays an important role in IgE regulation. The modulation of CD23 expression during specific immunotherapy (SIT) has been described previously. In the present study, we investigated in detail the effects of complete birch pollen allergen extract (BPA) on CD23 expression of peripheral blood mononuclear cells (PBMCs) in vitro. METHODS: PBMCs from 14 birch pollen-allergic (bp-allergic) patients and eight non-bp-allergic controls were stimulated with IL-4 and increasing doses of BPA. CD23 expression on monocytes and B cells was measured by flow cytometry; sCD23 release and the levels of IFN-gamma and IL-10 secretion were determined by ELISA. To analyse the mechanisms on CD23 expression in more detail, neutralizing anti-IFN-gamma and anti-IL-10 antibodies were added to IL-4 and BPA-stimulated cultures. RESULTS: IL-4 induced CD23 expression on B cells and on monocytes and sCD23 release in the bp-allergic and non-bp-allergic groups. The addition of BPA to IL-4-stimulated PBMC decreased CD23 expression significantly and dose-dependently on B cells in both groups. CD23 expression on monocytes was also decreased in both groups after the addition of BPA, but higher doses were required in the non-bp-allergic population. IL-4-induced sCD23 release was also significantly decreased after the addition of BPA. IFN-gamma and IL-10 were induced by BPA in both the bp-allergic and non-bp-allergic groups. The addition of neutralizing anti-IFN-gamma antibodies increased CD23 expression on B cells, which were stimulated with IL-4 and BPA, but had no effect on monocytes, whereas the addition of anti-IL-10 antibodies increased CD23 expression on monocytes but not on B cells. CONCLUSION: These data indicate that early immunological effects like down-regulation of CD23 on B cells and monocytes, which are observed during SIT are dose dependent, mediated by IFN-gamma and IL-10 and seem not to depend per se on the sensitization state of an individual.

Novel unconventional therapeutic approaches to atopic eczema.

Atopic eczema is a chronic, recurrent, multifactorial skin disease, and, accordingly, there are numerous therapeutic options for its symptomatic treatment. Conventional medications are however often unsatisfactory for many patients because of adverse effects on long-term use. For this reason, patients often readily welcome unconventional therapeutic approaches. We present here a selected number of such treatment modalities, namely gamma-linolenic acid, Chinese herbal tea, diets eliminating allergens, pseudoallergens, metal salts and sodium, and bioresonance. When stringent scientific criteria are applied in the evaluation of such study results, none of the reviewed alternative treatments provides unequivocal, convincing evidence of its efficacy, even when double-blind, placebo-controlled studies are available. With Chinese herbal tea, potentially serious adverse effects should be considered as well. Any new type of unconventional therapy should thus be thoroughly evaluated and shown to be equal or superior to conventional treatments with regard to both efficacy and tolerability before it is recommended for use in clinical practice.

Expression of growth factor receptors on human melanoma cells: comparison of modulating effects of interferons and retinoids.

Autocrine and paracrine growth factors are important mediators in malignant transformation. Interferons (IFN) and retinoids (RX) are well-known differentiative and immunomodulating agents with effects on subsets of different human tumors including malignant melanoma. In this study, we examined the modulating effects of three IFN and seven different RX on human melanoma cell lines regarding growth factor receptor expression. Growth factor receptor expression, including PDGF-R, NGF-R, EGF-R, IR, IGF-I-R, TFR and c-kit, was studied by immunohistochemistry and FACSscan analysis. Both groups of substances modulated the expression of some growth factor receptors. Upregulation of PDGF-R was seen after treatment with IFN as well as with RX. In contrast, EGF-R was found to be downregulated in two EGF-R-positive cell lines by IFN and, on the other hand, induced by RX in two EGF-R-negative cell lines. The expression of NGF-R was modulated ambiguously by these substances but demonstrated a cell line specificity in the different melanoma cell lines tested. Additionally, some of the tested growth factor receptors were not markedly changed regarding their expression by treatment with IFN and RX (IR, IGF-I-R, c-kit, TFR).