Role of cytokines in experimental colitis: relation to intestinal permeability.
There is now clear evidence supporting the role of cytokines in the clinical and immunopathological manifestations of human inflammotory bowel disease. The purpose of the present study was to determine the possible role of a cytokine network in a rat model of trinitrobenzene sulfonic acid-induced colitis and to examine its relation to intestinal permeability. After a rapid increase in the intestinal permeability of Evans blue in the colon, tumor necrosis factor-alpha increased transiently, and interleukin-1 and interleukin-6 followed thereafter. The majority of tumor necrosis factor-alpha- and interleukin-1-producing cells observed by immunofluorescent staining was revealed to be macrophages. Repeated injections of interleukin-1 receptor antagonist led to a modest decrease in myeloperoxidase activity and colon weight. These findings suggest that enhanced pro-inflammatory cytokine production from intestinal macrophages accompanied by increased intestinal permeability may contribute to intestinal and systemic features of trinitrobenzene sulfonic acid-induced colitis. Pharmacologic blockade of pro-inflammatory cytokines may help reduce intestinal inflammation.
Tateishi
H
H
Second Department of Medicine, Kurume University School of Medicine, Japan.
Mitsuyama
K
K
Toyonaga
A
A
Tomoyose
M
M
Tanikawa
K
K
D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D004396:Coloring Agents; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000502:physiology*; D004195:Disease Models, Animal; D005070:Evans Blue; D005500:Follow-Up Studies; D007150:Immunohistochemistry; D053590:Interleukin 1 Receptor Antagonist Protein; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid
D000209:Acute-Phase Proteins; D004396:Coloring Agents; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D005070:Evans Blue; D014302:Trinitrobenzenesulfonic Acid