SUMMARYThe role of cytokines in human hydatidosJs (Echinococcus granulosus infcciion) was evaluated in immunoassays determining pr(xiuciion of lL-4. IL-IO and interferon-gamma (IFN-f) in peripheral blood mononuclear cell (PBMC) cultures from .W hydalid patients and 14 uninfecled controls. In ceil cultures from hydatid paiients parasite and non-parasite antigen stimulation significantly increased IL-4 produclion (/• < 0005). Spontaneous and milogen-driven IL-4 production was similar in patients and controls. IL-10 and IFN--y production did not differ statistically in the two groups, even though some hydatid paiients produced these cytokines in large amounts. Notably, antigen-driven IFN-7 concentrations were invariably higher in patients than in uninfected controls. Data analysis showed a relationship belween IgE and IgG4 responses and parasitedriven cytokine production. High IgE and IgG4 responders produced high IL-4 and IL-10 concentrations. High IgE responders showed decreased IFN-7 production, but high lgG4 responders had IFN-7 levels slightly higher than those of low responders. Cytokine response patterns did not relate to the clinical stage of disease. The significantly increased IL-4 and the high IL-10 concentrations found in PBMC from many hydatid patients in this study are consistent with Th2 cell activation in human hydatidosis. The presence of anligen-driven IFN-7 production in paiients with E. granulosus infection implies concurrent intervention of the Th 1 or ThO cell subset.
A large portion of the IgE reactivity of Cupressaceae-allergic subjects appears to be associated with sugar moieties of C. arizonica extract which appear to be shared by bromelain and phospholipase A2, thus suggesting that the IgE of patients reacting with such epitopes probably react with beta 1 --> 2 xylose, alpha 1 --> 3 fucose and/or alpha 1 --> 6 fucose.
Beauvericin (BEA) and Enniatins (ENN) are mycotoxins produced by Fusarium fungi detected in food and feed; there are insufficient data to establish their reference values. To evaluate BEA and ENN oral toxicity, an integrated approach was applied. Among ENN, Enniatin B (ENNB) was selected as test substance. The approach is composed by: i) in vitro and acute in vivo genotoxicity tests; ii) a repeated‐dose oral toxicity study focused on genotoxic, immune, endocrine, nervous endpoints and the reproductive/developmental toxicity screening. For BEA, all the genotoxicity endpoints yielded negative results excluding Comet assay in duodenum and kidney after repeated doses. BEA immunotoxicity was observed in female mice, concentrated in number and functional activity of effector T cells in the spleen. Based on the repeated‐dose BEA study, the No Observed Adverse Effect Level (NOAEL) for female mice is 1 mg/kg b.w. per day (increased thyroid pycnotic nuclei and endometrial hyperplasia). In males, the NOAEL is 0.1 mg/kg b.w. per day (reduced colloid and altered T4 serum levels). Maternal NOAEL is 0.1 mg/kg b.w. per day (increased thymus weight), developmental NOAEL is 10 mg/kg b.w. per day. For ENNB, the results support a genotoxic effect in bone marrow and liver cells after acute treatment, but not after repeated exposure. Immunotoxic ENNB effects were observed in both genders, suggestive of a suppressive/inhibiting activity particularly evident in males. Based on the repeated‐dose ENNB study, the NOAEL for females is 0.18 mg/kg b.w. per day (histomorphometrical effects on thymus, uterus and spleen). In male mice, the NOAEL is 1.8 mg/kg b.w. per day (enterocyte vacuolization in duodenum and increased Reactive Oxygen Species and reduced Glutathione brain levels). The maternal NOAEL is 1.8 mg/kg b.w. per day (decreased white pulp area and increased red/white pulp area ratio in spleen), developmental NOAEL is 18 mg/kg b.w. per day.
Probiotic bacteria as modulators of the immune response have been intensively studied in reducing the risk of immune-mediated diseases, including atopic diseases. Results from in vitro studies demonstrated that probiotics may modify the polarization of immune cells, supporting potential therapeutic effects in atopic diseases. Several clinical studies have been designed to explore the effective role of probiotics in the modulation of allergic diseases. The results of these studies, although promising, are not conclusive yet and are considered insufficient to recommend probiotics as a part of standard therapy in any allergic conditions. In vivo studies on animal models can provide useful information on the immunologic mechanisms responsible for the potential antiallergic effects of probiotic bacteria. The immunomodulatory activity of the probiotic mixture VSL#3 has been studied in the mouse models of allergic sensitization and anaphylaxis developed in our laboratory with inhalant and food allergens, according to a prophylactic setting by the intranasal route (inhalant allergy model) or a therapeutic setting by the oral route (food allergy model). Intranasally delivered probiotic bacteria prevented the development of Parietaria major allergen-specific response, by down-regulating T helper cell 2 responses at the local and systemic level. Oral therapeutic treatment was able to reduce both systemic and local anaphylactic symptoms induced by oral challenge with the sensitizing allergen Shrimp Tropomyosin. The induction of protective immune responses at the sites of allergen exposure linked to counterregulatory local and systemic immune responses by mucosal delivery of probiotic bacteria mixtures might become an effective strategy in the prevention and therapy of allergic diseases.
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