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.

Background: Nonpathogenic Escherichia coli strain Nissle 1917 (EcN) has immunomodulatory properties and can act on different cells which are important for the allergic immune response. Herein, we investigated the efficacy and tolerability of EcN in subjects with grass pollen-dependent allergic rhinoconjunctivitis. Methods: Grass pollen-allergic subjects were randomly allocated to receive EcN in a double-blind, placebo-controlled manner. The treatment was performed from 2 months before onset until the end of one grass pollen season (in total: 6 months). The clinical symptom score and the intake of symptomatic medications were assessed. A skin prick test and grass pollen-specific immunoglobulin (Ig) E and IgA were evaluated before and after treatment. Results: Our results show that coseasonal treatment with EcN in grass pollen-allergic subjects was not superior to placebo as assessed using the symptom-medication score (p = 0.257). Interestingly, an increase [median (range)] in grass pollen-specific IgA was detectable in the EcN group [20,556 LU/ml (1,812-60,800)] versus placebo [5,246 LU/ml (944-50,467)] (p = 0.048). Conclusions: The results indicate that 6 months of coseasonal nonspecific immunomodulation by EcN is not sufficient to achieve clinical efficacy in grass pollen-allergic subjects. Future approaches in which such immunomodulators are combined with an allergen-specific protocol might enhance the clinical efficacy of the allergen-specific treatment.

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Bacterial stimulation plays an important role in modulating the allergic immune response. The aim of this study was to investigate the effects of inactivated probiotic Lactobacillus acidophilus and non-pathogenic Escherichia coli strain Nissle on the phenotype and function of T- and B-cells. Peripheral blood mononuclear cells from patients with grass-pollen allergy (n=10) and non-allergic patients (n=19) were co-stimulated with inactivated bacteria and grass-pollen allergen. Expression of CD23, CD80, CD86 and CD69 were analysed, and the intracellular production of interleukin-4 and interferon-gamma was measured by direct ex vivo flow cytometry after stimulation. Both bacteria induced a significant up-regulation of CD69 expression on T-lymphocytes (p=0.001). CD23 expression was significantly increased following stimulation with allergen (p=0.008), but reduced after stimulation with Lactobacillus and significantly reduced with E. coli plus allergen (p=0.029). CD80 expression was reduced after stimulation with Lactobacillus in the allergic group only (p=0.021). By contrast, CD86 expression was significantly increased after stimulation with Lactobacillus (p=0.049) and distinctly increased with E. coli in both groups (p=0.001). The cytokine patterns of CD69-positive T-lymphocytes from allergic patients showed a TH2-dominated response after allergen stimulation (interferon-gamma/interleukin-4-ratio 0.2), directed into a T-helper1-like response by stimulation with both types of bacteria (interferon-gamma/interleukin-4-ratios 1.5-2.0 in both groups). These data show that both types of bacteria modulate the allergic immune response by the alteration of CD23 and co-stimulatory molecule expression. Regarding cytokine production, the data suggest a differential response to both bacteria depending on the atopic state, but a clear promotion of T-helper1-dominated response in allergic donors.

We demonstrate that miltefosine is locally active in patients with AD and led to a sustained clinical improvement in local skin inflammation. Moreover, the increased frequency of FoxP3(+) cells in the skin of patients with AD suggests its immunomodulatory properties.

Anti-thymocyte globulin (ATG) is used in the treatment of acute organ rejection. We studied in vitro the effect of low-dose ATG on B-cell activation and differentiation to antibody-secreting cells, as this may have an effect on B cell-driven autoimmune diseases, such as pemphigus vulgaris. Immunoglobulin production was analysed in the supernatants of peripheral blood mononuclear cells (PBMC) and CD19+ B cells from healthy donors and from patients with different autoimmune diseases. B-cell proliferation, viability and differentiation were analysed using flow cytometry. Differentiation of B cells to immunoglobulin G (IgG) secreting cells was significantly reduced by ATG, but not by control unspecific IgG from non-immunized rabbits (rIgG). B-cell viability was not altered by sub-depleting concentrations of ATG. In contrast, B-cell proliferation was enhanced by ATG. When PBMC from patients with autoimmune diseases were studied, specific autoantibodies could be detected in 1 out of 10 patients. In this patient, who had pemphigus vulgaris, ATG not only decreased total IgG, but decreased also specific anti-desmoglein-3. In conclusion, these data suggest that ATG at low concentrations inhibits B-cell differentiation and function.

Our data demonstrate that, in vitro, immunoglobulins modulate the activation and cytokine production of peripheral blood lymphocytes from both HD and patients with AD.

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