Plasma exudation, hyperaemia, and epithelial permeability in rats with oxazolone-induced colitis: modulatory effects of budesonide.
BACKGROUND
Oxazolone-induced colitis in the rat is an immune-driven model of human colitis. The aim of the present study was to measure the changes in the absorptive and exudative permeabilites, oedema formation, and local blood flow in this model during the development of inflammation. We also assessed the effects of acute (<1 h), topical glucocorticosteroid (GCS) treatment on these factors.


METHODS
Colitis was induced by local instillation of oxazolone in previously sensitized animals. Calculating the 40-min plasma-equivalent extravascular volume quantitated the plasma exudation rate. This was determined by using labelled albumin as marker for total tissue content of plasma and Evans blue content as marker for the intravascular volume. Absorptive permeability was simultaneously measured as uptake of rectally administered (51Cr)-labelled ethylenediaminetetraacetic acid (EDTA). In separate experiments regional blood flows were measured by means of the labelled microsphere method.


RESULTS
At both 3 and 24 h after challenge marked enhancements of both exudative and absorptive permeabilities were found. At 24 h there was also an increase in local blood flow. GCS treatment abolished all of the hyperaemia and the main part of the exudative response but had no significant effect on the absorptive permeability.


CONCLUSIONS
In this model immunologic mechanisms induce permeability and blood flow changes similar to those in the human disease. It seems suitable for the study of GCS and other anti-inflammatory or immune-modulating drugs.
Ekström
G M
GM
Dept. of Immunopharmacology, AstraZeneca R&D, Lund, Sweden.
Andersson
S E
SE
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003106:Colon / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004492:Edetic Acid / Q000493:pharmacokinetics; D004727:Endothelium / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D007421:Intestine, Small / Q000098:blood supply; D010081:Oxazolone; D010539:Permeability; D051381:Rats
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D010081:Oxazolone; D019819:Budesonide; D004492:Edetic Acid