The tripeptide FEG ameliorates systemic inflammatory responses to rat intestinal anaphylaxis.
BACKGROUND
Food allergies are generally associated with gastrointestinal upset, but in many patients systemic reactions occur. However, the systemic effects of food allergies are poorly understood in experimental animals, which also offer the opportunity to explore the actions of anti-allergic drugs. The tripeptide D-phenylalanine-D-glutamate-Glycine (feG), which potentially alleviates the symptoms of systemic anaphylactic reactions, was tested to determine if it also reduced systemic inflammatory responses provoked by a gastric allergic reaction.


RESULTS
Optimal inhibition of intestinal anaphylaxis was obtained when 100 microg/kg of feG was given 20 min before the rats were challenged with antigen. The increase in total circulating neutrophils and accumulation of neutrophils in the heart, developing 3 h and 24 h, respectively, after antigen challenge were reduced by both feG and dexamethasone. Both anti-inflammatory agents reduced the increase in vascular permeability induced by antigen in the intestine and the peripheral skin (pinna), albeit with different time courses. Dexamethasone prevented increases in vascular permeability when given 12 h before antigen challenge, whereas feG was effective when given 20 min before ingestion of antigen. The tripeptide prevented the anaphylaxis induced up regulation of specific antibody binding of a cell adhesion molecule related to neutrophil activation, namely CD49d (alpha4 integrin).


CONCLUSIONS
Aside from showing that intestinal anaphylaxis produces significant systemic inflammatory responses in non-intestinal tissues, our results indicate that the tripeptide feG is a potent inhibitor of extra-gastrointestinal allergic reactions preventing both acute (30 min) and chronic (3 h or greater) inflammatory responses.
Turesin
Fusun
F
Faculty of Medicine, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta T2N 4N1. fturesin@ucalgary.ca
Sadr
Aida
A
Davison
Joseph S
JS
Mathison
Ronald
R
D000707:Anaphylaxis / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D000818:Animals; D030161:Avian Proteins / Q000276:immunology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D018821:CD18 Antigens / Q000096:biosynthesis / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000378:metabolism; D002645:Chickens; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D007583:Jejunum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*
D030161:Avian Proteins; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D009842:Oligopeptides; C114891:tripeptide FEG; D010047:Ovalbumin