Increased Intestinal Permeability in Atopic Eczema

Pike, Michael; Heddle, Richard; Boulton, P; Turner, Malcolm; Atherton, D.J.

doi:10.1111/1523-1747.ep12284035

Cited by 115 publications

(72 citation statements)

References 18 publications

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“…Further studies are necessary to determine why the dermatitis develops in only about one third of mice with food allergy and what immunopathogenic mechanisms are responsible for the skin eruption. It will also be of interest to determine whether these mice have gastrointestinal symptoms and malabsorption, as reported in children with food allergy, [50][51][52] and whether they have airway hyperreactivity, as noted in human subjects 53 and dogs. 14 With a better understanding of the relationship between food hypersensitivity and AD, more effective forms of therapy may be developed.…”

Section: Discussionmentioning

confidence: 99%

Murine model of atopic dermatitis associated with food hypersensitivity

Kleiner²,

Huang³

et al. 2001

Journal of Allergy and Clinical Immunology

109

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Background: Atopic dermatitis (AD) is an eczematous skin eruption that generally begins in early infancy and affects up to 12% of the population. The cause of this disorder is not fully understood, although it is frequently the first sign of atopic disease and is characterized by an elevated serum IgE level, eosinophilia, and histologic tissue changes characterized early by spongiosis and a CD4 + T H 2 cellular infiltrate. Hypersensitivity to foods has been implicated as one causative factor in up to 40% of children with moderate-to-severe AD. Objective: The purpose of this study was to establish a murine model of food-induced AD. Methods: Female C3H/HeJ mice were sensitized orally to cow's milk or peanut with a cholera toxin adjuvant and then subjected to low-grade allergen exposure. Histologic examination of skin lesions, allergen-specific serum Ig levels, and allergen-induced T-cell proliferation and cytokine production were examined. Atopic dermatitis (AD) is a form of eczema that generally begins in early infancy and is characterized by extreme pruritus, chronically relapsing course, and distinctive distribution. AD is often the first sign seen in a child who is prone to atopic disease, with 50% of all AD developing in the first year of life and 80% developing by 5 years of age. 1 In chronic skin lesions the epidermis has moderate-to-marked hyperplasia, with elongation of the rete ridges and prominent hyperkeratosis. Spongiosis is variable, and the numbers of mast cells and Langerhans cells are significantly increased. 2,3 Eosinophils are sparse, although eosinophil products (major basic protein) are prominent. 4 Although the pathogenic role of allergy in AD has been debated for over a century, clinical studies over the past 2 decades have supported the pathogenic role of food allergy in a subset of patients with AD. 5-7 A recent study found that approximately 40% of children with moderate-to-severe AD attending a university dermatology clinic had food hypersensitivity. 7 Other studies delineating the role of IgE-bearing antigen-presenting cells in establishing T H 2 lymphocytic responses 8 and demonstrating the predominant T H 2-lymphocytic infiltrate in acute eczematous lesions 9 have provided further support for the pathogenic role of allergy in AD.Animal models provide powerful tools for dissecting pathogenic mechanisms responsible for various disorders. A number of murine models of asthma have been developed in the past several years that have contributed greatly to our understanding of the immunopathogenesis of allergen-induced asthma. 10-12 Models of antigenassociated AD have been reported in cats and dogs, but because of difficulties with consistent induction of ADlike eruptions and high expense, they have not been widely studied. 13,14 A mouse strain, NC/Nga, has been reported that spontaneously has an AD-like skin lesion and IgE hyperproduction, presumably triggered by environmental factors. 15 More recently, a murine model of AD was described in which BALB/c mice were sensitized to ovalbumin (OVA...

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Section: Discussionmentioning

confidence: 99%

Murine model of atopic dermatitis associated with food hypersensitivity

Kleiner²,

Huang³

et al. 2001

Journal of Allergy and Clinical Immunology

109

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“…Similarly in the diarrhea-predominant form of IBS, altered permeability of the epithelium is thought to increase the load of bacterial and dietary antigens in the lamina propria, leading to the activation of mucosal immune responses involved in the generation of diarrhea and visceral hypersensitivity (1). Altered intestinal epithelial permeability is also associated with diabetes, celiac disease, diarrhea in HIV-infected patients, atopic eczema, and altered sensitivity to food allergens (8,9,30,31,44). Consequently, modulation of epithelial permeability is a highly relevant target for novel therapeutic or prophylactic treatments against a range of diseases.…”

Section: Translational Highlights This Study Demonstrates That In Thmentioning

confidence: 99%

Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier

Karczewski

Troost

Konings

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

529

390

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Karczewski J, Troost FJ, Konings I, Dekker J, Kleerebezem M, Brummer RM, Wells JM. Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. Am J Physiol Gastrointest Liver Physiol 298: G851-G859, 2010. First published March 11, 2010; doi:10.1152/ajpgi.00327.2009.-Lactobacillus plantarum, a commensal bacterium of humans, has been proposed to enhance the intestinal barrier, which is compromised in a number of intestinal disorders. To study the effect of L. plantarum strain WCFS1 on human barrier function, healthy subjects were administered L. plantarum or placebo in the duodenum for 6 h by means of a feeding catheter. The scaffold protein zonula occludens (ZO)-1 and transmembrane protein occludin were found to be significantly increased in the vicinity of the tight-junction (TJ) structures, which form the paracellular seal between cells of the epithelium. In an in vitro model of the human epithelium, L. plantarum induced translocation of ZO-1 to the TJ region; however, the effects on occludin were minor compared with those seen in vivo. L. plantarum was shown to activate Toll-like receptor 2 (TLR2) signaling, and treatment of Caco-2 monolayers with the TLR2 agonist Pam 3 -Cys-SK4(PCSK) significantly increased fluorescent staining of occludin in the TJ. Pretreatment of Caco-2 monolayers with L. plantarum or PCSK significantly attenuated the effects of phorbol ester-induced dislocation of ZO-1 and occludin and the associated increase in epithelial permeability. Our results identifying commensal bacterial stimulation of TLR2 in the gut epithelium as a regulator of epithelial integrity have important implications for understanding probiotic mechanisms and the control of intestinal homeostasis. epithelium; intestine

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“…These findings might reflect mucosal damage caused by local hypersensitivity mechanisms. In patients with cutaneous symptoms, however, modifications in the intestinal barrier remain elusive (4)(5)(6)(7). Contradictory results may be attributable to different types of immunologic reactions operative in CMA, with varying components of local and systemic responses.…”

mentioning

confidence: 99%

Local Immune Response Measured in Blood Lymphocytes Reflects the Clinical Reactivity of Children with Cow's Milk Allergy

Isolauri

Virtanen²,

Jalonen

et al. 1990

Pediatr Res

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ABSTRACT. Study was made of immune responses in cow's milk allergy by a new immunoassay that measures total Ig-secreting cells and specific antibody-secreting cells during their maturation cycle in peripheral blood. These primed gut-associated lymphoid tissue-derived lymphocytes are assumed to reflect the intestinal immune responses. During diagnostic milk provocation, 15 patients had acute urticarial skin eruptions, eight patients had slow onset of eczema, and 15 showed symptoms from the gastrointestinal tract. A significant increase in IgM-secreting cells (means with 95% confidence intervals) from 382.2

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Increased Intestinal Permeability in Atopic Eczema

Cited by 115 publications

References 18 publications

Murine model of atopic dermatitis associated with food hypersensitivity

Murine model of atopic dermatitis associated with food hypersensitivity

Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier

Local Immune Response Measured in Blood Lymphocytes Reflects the Clinical Reactivity of Children with Cow's Milk Allergy

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