Effect of methylprednisolone on the ulceration, matrix metalloproteinase distribution and eicosanoid production in a model of colitis in the rabbit.
This study has examined the response of a rabbit model of inflammatory bowel disease to methylprednisolone. Colitis was induced in the colon of rabbits with 40 mg trinitrobenzenesulphonic acid in 25% ethanol (TNBS). The effect of methylprednisolone (0.5 mg/kg/day) on the development of colitis was determined at one week, by examining the colon's macroscopic and microscopic appearance, the distribution of matrix metalloproteinases (MMPs) and by measuring eicosanoid production. Although there was no difference in the area of ulcerated colonic tissue in the treated and untreated TNBS animals, the increase in polymorphonuclear leucocytes was significantly reduced in TNBS rabbits given methylprednisolone. The only difference in the distribution of MMPs was a reduction in the number of polymorphonuclear leucocytes containing gelatinase B. The release of immunoreactive PGE2 and LTB4, but not 6-keto PGF1 alpha, was increased in the TNBS animals and was unchanged by methylprednisolone. These results show that methylprednisolone does not modify the injury produced by TNBS in this model despite reducing the infiltration of polymorphonuclear leucocytes. Hence it suggests that these cells do not contribute to the injury observed, are not the source of the eicosanoids and that gelatinase B is not required in the healing process in this model.
Anthony
D
D
Department of Surgery, University College London Medical School, UK.
Savage
F
F
Boulos
P
P
Hembry
R
R
Sams
V
V
Trevethick
M
M
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism*; D007958:Leukocyte Count; D007975:Leukotriene B4 / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism*; D008775:Methylprednisolone / Q000627:therapeutic use*; D009504:Neutrophils / Q000473:pathology; D011817:Rabbits; D011897:Random Allocation; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D015777:Eicosanoids; D007975:Leukotriene B4; D015121:6-Ketoprostaglandin F1 alpha; D014302:Trinitrobenzenesulfonic Acid; D008666:Metalloendopeptidases; D015232:Dinoprostone; D008775:Methylprednisolone