Immune control of food intake: enteroendocrine cells are regulated by CD4+ T lymphocytes during small intestinal inflammation

Background and aims: Gastrointestinal inflammation reduces food intake but the biological mechanisms explaining suppressed feeding during inflammation are unknown. We have used a model of upper gut infection (Trichinella spiralis in the mouse) to study the effect of inflammation on food intake, and...

Full description

Saved in:
Bibliographic Details
Published in:Gut 2006-04, Vol.55 (4), p.492-497
Main Authors: McDermott, J R, Leslie, F C, D’Amato, M, Thompson, D G, Grencis, R K, McLaughlin, J T
Format: Article
Language:English
Subjects:
5-HT
5-hydroxytryptamine
Animals
appetite regulation
Biological and medical sciences
CCK
Cell Count
cholecystokinin
Cholecystokinin - immunology
Cytokines - immunology
Disease Models, Animal
Duodenum - cytology
Duodenum - immunology
Eating - immunology
EEC
endocrine cells
enteroendocrine cell
Enteroendocrine Cells - immunology
Feeding and Eating Disorders - immunology
Feeding and Eating Disorders - parasitology
Food
Gastroenterology. Liver. Pancreas. Abdomen
Immunohistochemistry - methods
Infections
Inflammation
interleukin
Interleukins - immunology
Intestine, Small - immunology
Mast Cells - immunology
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Inbred Strains
Neurogastroenterology
Parasites
Receptors, Cholecystokinin - antagonists & inhibitors
Rodents
Small intestine
Studies
Th2 Cells - immunology
Trichinella spiralis
Trichinella spiralis - immunology
Trichinellosis - immunology
Tropical diseases
VCU
villus-crypt unit
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background and aims: Gastrointestinal inflammation reduces food intake but the biological mechanisms explaining suppressed feeding during inflammation are unknown. We have used a model of upper gut infection (Trichinella spiralis in the mouse) to study the effect of inflammation on food intake, and explored the role of a key enteroendocrine cell (EEC) in the regulation of feeding by the immune response. Methods: Food intake of NIH mice infected with the intestinal nematode Trichinella spiralis was measured. Duodenal cholecystokinin (CCK) cells were counted. Plasma CCK was measured. Infected mice were treated with a specific CCK1 receptor antagonist, and food intake reassessed. The influence of the immune response on food intake and CCK was mechanistically examined by treating mice with CD4 or mast cell neutralising antibodies. The role of the T helper 2 response was further explored in mice genetically deficient for interleukin (IL)-4, IL-13, or IL-4Rα (receptor α subunit). Results: Food intake of infected mice was significantly reduced at the temporal peak of intestinal inflammation. CCK expressing EEC were upregulated in infected mice, and plasma CCK levels were increased. A CCK1 receptor antagonist restored the food intake of infected mice to a significant degree. Furthermore, suppression of food intake was completely abolished in the absence of CD4+ T lymphocytes or IL-4Rα. Conclusions: The data show for the first time that intestinal inflammation results in reduced food intake due to upregulation of CCK. Moreover, following infection, food intake and CCK expressing cells are under the specific control of CD4+ T-cells, via release of IL-4 and IL-13.
ISSN:0017-5749
1468-3288
DOI:10.1136/gut.2005.081752