Food allergy alters jejunal circular muscle contractility and induces local inflammatory cytokine expression in a mouse model.
BACKGROUND
We hypothesized that food allergy causes a state of non-specific jejunal dysmotility. This was tested in a mouse model.


METHODS
Balb/c mice were epicutaneously sensitized with ovalbumin and challenged with 10 intragastric ovalbumin administrations every second day. Smooth muscle contractility of isolated circular jejunal sections was studied in organ bath with increasing concentrations of carbamylcholine chloride (carbachol). Smooth muscle layer thickness and mast cell protease-1 (MMCP-1) positive cell density were assayed histologically. Serum MMCP-1 and immunoglobulins were quantified by ELISA, and mRNA expressions of IFN-gamma, IL-4, IL-6 and TGFbeta-1 from jejunal and ileal tissue segments were analyzed with quantitative real-time PCR.


RESULTS
Ovalbumin-specific serum IgE correlated with jejunal MMCP-1+ cell density. In the allergic mice, higher concentrations of carbachol were required to reach submaximal muscular stimulation, particularly in preparations derived from mice with diarrhoea. Decreased sensitivity to carbachol was associated with increased expression of IL-4 and IL-6 mRNA in jejunum. Smooth muscle layer thickness, as well as mRNA of IFN-gamma and TGF-beta1 remained unchanged.


CONCLUSIONS
In this mouse model of food allergy, we demonstrated a decreased response to a muscarinic agonist, and increased levels of proinflammatory IL-6 and Th2-related IL-4, but not Th1-related IFN-gamma mRNAs in jejunum. IgE levels in serum correlated with the number of jejunal MMCP-1+ cells, and predicted diarrhoea. Overall, these changes may reflect a protective mechanism of the gut in food allergy.
Valeur
Jørgen
J
Institute of Medicine, University of Bergen, Bergen, Norway. jorgen.valeur@med.uib.no
Lappalainen
Jani
J
Rita
Hannu
H
Lin
Aung Htun
AH
Kovanen
Petri T
PT
Berstad
Arnold
A
Eklund
Kari K
KK
Vaali
Kirsi
K
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005512:Food Hypersensitivity / Q000378:metabolism / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000502:physiology; D007082:Ileum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000473:pathology / Q000503:physiopathology*; D010047:Ovalbumin / Q000009:adverse effects*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D018678:Cholinergic Agents; D016207:Cytokines; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D007371:Interferon-gamma; D002217:Carbachol; D010047:Ovalbumin