Lactobacillus rhamnosus HN001 Attenuates Allergy Development in a Pig Model

HN001 (HN001) supplementation decreased the prevalence of eczema and IgE associated eczema. However, the influence of HN001 on the incidence of wheeze, asthma, and/or other allergic manifestations has yet to be reported.This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model. allergen (ASA) during a six week time frame in post-weanling pigs supplemented daily with HN001, or without supplementation. One week following final sensitization intradermal skin tests and respiratory challenges were conducted.In response to intradermal and respiratory challenges, ASA-sensitized pigs fed HN001 had less severe skin flare reactions, smaller increases in pleural pressure, and trends towards lower changes in arterial oxygen and carbon dioxide partial pressure levels compared to control pigs. The frequency of ASA-specific IFN-γ-secreting peripheral blood mononuclear cells, as well as the amount of IL-10 produced by ASA-specific cells, was of greater magnitude in probiotic-fed pigs compared to control animals. These observations suggest that differences in clinical responses to the allergen challenges may be related to probiotic-induced modulation of Th1 (IFN-γ) and regulatory (IL-10) cytokine expression.Probiotic supplementation decreased the severity of allergic skin and lung responses in allergen-sensitized pigs with a corresponding increase in IFN-γ expression. A similar correlation between certain allergic responses and increased IFN-γ expression has been reported in human clinical studies of allergy; this pig model of allergy may be indicative of potential probiotic modulation of allergic lung disease in humans

Allergen-induced late airways reaction in the pig : influence of endogenous and exogenous glucocorticoids

A novel model for studies of the allergen-induced late reaction in the lower airways was developed in the pig. The influence on late bronchial obstruction and granulocyte function of endogenous cortisol levels and treatment with the glucocorticoid budesonide (BUD) was evaluated. In anaesthetized and mechanically ventilated pigs actively-sensitized to Ascaris suum allergen,challenge in the lower airways caused an acute increase in total lung resistance lasting approximately 1 h. A late bronchial obstruction starting 3.5-4 h after allergen challenge was seen in pigs treated with the cortisol-synthesis inhibitor metyrapone, but not in pigs with high cortisol levels obtained in response to stress due to anaesthesia and surgical manipulation. Bloodflow in the bronchial circulation was measured, and both acute and late decrease in bronchialvascular resistance was seen, the latter even if late bronchial obstruction was absent. An increase of the urinary metabolites of the mast cell-derived mediators histamine and leukotriene (LT) C 4(i.e. methylhistamine and LTE4, respectively) was detected during the acute reaction and this increase correlated with the magnitude of the acute bronchial obstruction. No late increase in urinary methylhistamine was seen, but late increases in LTE4 were seen in some of the pigs with late airways reactions. Eosinophil peroxidase (EPO) was purified from Ascaris suum-infested pigs and was used to raise polyclonal antibodies recognizing porcine eosinophils by immunostaining techniques. Neutrophils in lung tissue were detected by antibodies raised against porcine myeloperoxidase (MPO). Released EPO and MPO were detected in bronchoalveolar lavage (BAL) fluid by newly developed immunoassays. A blood eosinophilia starting 4 h after allergen challenge was seenand at 8 h eosinophils were increased in lung parenchyma, around bronchioles and in BAL fluid. An increase in the activation marker EPO was also detected in BAL fluid at 8 h.Neutrophil infiltration around bronchioles was not increased after allergen challenge, even though higher numbers of neutrophils were found in BAL fluid. The levels of MPO in BALfluid were increased in some animals only. High doses of BUD (50 µg kg-l, i.v.) given 3 h and 0.5 h before allergen challenge inhibited the late bronchial obstruction, cysteinyl LT release, blood eosinophilia, and eosinophil infiltration and activation, and reduced the number of neutrophils in BAL fluid. BUD in clinically relevant, lower doses given as an aerosol (10 µg kg-l) or in equivalent doses as an i.v.infusion (5 µg kg-l ), 1 h before allergen challenge had similar effects on granulocyte infiltration and activation. However, the aerosol treatment inhibited the late bronchial obstruction and LTrelease, whereas the systemic treatment did not. In conclusion, the actively-sensitized pig seems to be a relevant model for studies of the allergen-induced late bronchial obstruction and activation of the eosinophil and neutrophil granulocyte. This model shows that the effect of BUD on late bronchial obstruction is locally mediated and that the late obstruction does not seem to be caused by granulocyte infiltration