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Lactobacillus rhamnosus HN001 attenuates allergy development in a pig model.

Thomas DJ, Husmann RJ, Villamar M, Winship TR, Buck RH, Zuckermann FA - PLoS ONE (2011)

Bottom Line: This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model.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.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.

View Article: PubMed Central - PubMed

Affiliation: Abbott Nutrition, Columbus, Ohio, United States of America. debra.thomas@abbott.com

ABSTRACT

Background: Probiotics have been studied as immunomodulatory agents of allergy. Several human probiotic trials tracking the development of eczema and other forms of allergy have yielded inconsistent results. A recent infant study demonstrated that pre and postnatal Lactobacillus rhamnosus 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.

Objective: This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model.

Methods: Allergy was induced by a series of subcutaneous and intratracheal sensitizations with Ascaris suum 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.

Results: 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.

Conclusions: 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.

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Lung tissue 24 hours post-respiratory challenge with ASA.Lungs were removed from a non-sensitized (A) and an ASA-sensitized (B) pig 24 hours after respiratory challenge, fixed in formalin, stained with hematoxylin and eosin, and examined with a light microscope (400X magnification). An increased cellular infiltrate, composed mainly of eosinophils (cells with a pink cytoplasm surrounding a blue nucleus), in airway submucosa and lamina propria is apparent in the tissue from the ASA-sensitized animal as compared to that from the naïve pig.
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pone-0016577-g002: Lung tissue 24 hours post-respiratory challenge with ASA.Lungs were removed from a non-sensitized (A) and an ASA-sensitized (B) pig 24 hours after respiratory challenge, fixed in formalin, stained with hematoxylin and eosin, and examined with a light microscope (400X magnification). An increased cellular infiltrate, composed mainly of eosinophils (cells with a pink cytoplasm surrounding a blue nucleus), in airway submucosa and lamina propria is apparent in the tissue from the ASA-sensitized animal as compared to that from the naïve pig.

Mentions: In previous non-intervention studies pigs sensitized with ASA and challenged intradermally or intratracheally with ovalbumin, or animals mock sensitized with phosphate buffered saline and challenged in a similar manner with ASA, did not exhibit dermal or respiratory reactions (data not shown). In contrast, an ASA intradermal challenge to ASA-sensitized animals is associated with a typical dermal inflammatory response that is characterized by reddening of the injection site within 5 minutes of exposure. The flare intensity increases, peaking by 20 minutes, and gradually wanes thereafter. To establish the nature of the skin flare response, tissue samples from reactive sites of several ASA-sensitized pigs challenged intradermally with 40 µg ASA 20 minutes earlier were stained with hematoxylin and eosin and examined microscopically. Histological evaluation of reactive skin sites indicated marked dermal and subcutaneous edema as well as perivascular infiltration by lymphocytes and eosinophils (data not shown). A similar examination of lung tissue samples from ASA intratracheally challenged pigs demonstrated the infiltration of eosinophils into the lamina propria of airway epithelium in ASA-sensitized animals only and not in ASA-naïve pigs (Figure 2A & B). Eosinophil infiltration of tissues is a hallmark of allergic responses and lung eosinophilia has been implicated as a factor of lung remodeling in asthma [14], [15].


Lactobacillus rhamnosus HN001 attenuates allergy development in a pig model.

Thomas DJ, Husmann RJ, Villamar M, Winship TR, Buck RH, Zuckermann FA - PLoS ONE (2011)

Lung tissue 24 hours post-respiratory challenge with ASA.Lungs were removed from a non-sensitized (A) and an ASA-sensitized (B) pig 24 hours after respiratory challenge, fixed in formalin, stained with hematoxylin and eosin, and examined with a light microscope (400X magnification). An increased cellular infiltrate, composed mainly of eosinophils (cells with a pink cytoplasm surrounding a blue nucleus), in airway submucosa and lamina propria is apparent in the tissue from the ASA-sensitized animal as compared to that from the naïve pig.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046142&req=5

pone-0016577-g002: Lung tissue 24 hours post-respiratory challenge with ASA.Lungs were removed from a non-sensitized (A) and an ASA-sensitized (B) pig 24 hours after respiratory challenge, fixed in formalin, stained with hematoxylin and eosin, and examined with a light microscope (400X magnification). An increased cellular infiltrate, composed mainly of eosinophils (cells with a pink cytoplasm surrounding a blue nucleus), in airway submucosa and lamina propria is apparent in the tissue from the ASA-sensitized animal as compared to that from the naïve pig.
Mentions: In previous non-intervention studies pigs sensitized with ASA and challenged intradermally or intratracheally with ovalbumin, or animals mock sensitized with phosphate buffered saline and challenged in a similar manner with ASA, did not exhibit dermal or respiratory reactions (data not shown). In contrast, an ASA intradermal challenge to ASA-sensitized animals is associated with a typical dermal inflammatory response that is characterized by reddening of the injection site within 5 minutes of exposure. The flare intensity increases, peaking by 20 minutes, and gradually wanes thereafter. To establish the nature of the skin flare response, tissue samples from reactive sites of several ASA-sensitized pigs challenged intradermally with 40 µg ASA 20 minutes earlier were stained with hematoxylin and eosin and examined microscopically. Histological evaluation of reactive skin sites indicated marked dermal and subcutaneous edema as well as perivascular infiltration by lymphocytes and eosinophils (data not shown). A similar examination of lung tissue samples from ASA intratracheally challenged pigs demonstrated the infiltration of eosinophils into the lamina propria of airway epithelium in ASA-sensitized animals only and not in ASA-naïve pigs (Figure 2A & B). Eosinophil infiltration of tissues is a hallmark of allergic responses and lung eosinophilia has been implicated as a factor of lung remodeling in asthma [14], [15].

Bottom Line: This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model.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.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.

View Article: PubMed Central - PubMed

Affiliation: Abbott Nutrition, Columbus, Ohio, United States of America. debra.thomas@abbott.com

ABSTRACT

Background: Probiotics have been studied as immunomodulatory agents of allergy. Several human probiotic trials tracking the development of eczema and other forms of allergy have yielded inconsistent results. A recent infant study demonstrated that pre and postnatal Lactobacillus rhamnosus 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.

Objective: This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model.

Methods: Allergy was induced by a series of subcutaneous and intratracheal sensitizations with Ascaris suum 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.

Results: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus