[The effect of interleukin-1 beta interleukin-8 in the pathogenesis of experimental colitis and evaluation of interleukin-1 receptor antagonist therapy].
OBJECTIVE
To study the effect of interleukin-1 beta and interleukin-8 in the pathogenesis of colitis and evaluate the therapeutic effect of interleukin-1 receptor antagonist(IL-1ra).


METHODS
A rat model of chronic experimental colitis was induced by administration of trinitrobenzenesulfonic acid (TNBS, 30 mg) in 50% ethanol 0.25 ml. IL-1ra was then administered intravenously with a dosage of 7 mg/kg at different times. Hydrocortisone (3 mg) i.v. administration was served as control. Tissue expression of IL-1 beta mRNA and IL-8 mRNA was then studied by in situ hybridization before and after IL-1ra administration. Histological examination and tissue myeloperoxidase (MPO) and superoxide dismutase (SOD) activities detection were also made to assess the severity of colitis.


RESULTS
An acute inflammation with ulcers, neutrophil infiltration and crypt abscess developed that evolved into a chronic inflammation with abundant fibrous connective tissue hypertrophy at 21 days. And it then recurs only after 10 mg TNBS administration. Activities of MPO and SOD correlated with severity of inflammation. Expression of IL-1 beta mRNA was detected in macrophages in lamina propria and submucosa during the whole period of inflammation. It could be also present in epithelial cells in the 3rd day of colitis. While IL-8 mRNA expression appeared at the 3rd day, and disappeared at 21th day when colitis turned into chronic. After IL-1ra administration, the expression of these two interleukins could not be detected, accompanied with alleviation of histological manifestation, decrease of MPO activity and elevation of SOD activity.


CONCLUSIONS
IL-1 beta and IL-8 were involved in the pathogenesis of colitis. IL-1ra has preventive and therapeutic effect to colitis.
Zhu
F
F
PUMC Hospital, CAMS and PUMC, Beijing 100730.
Qian
J
J
Pan
G
G
Quan
S
S
D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D000431:Ethanol; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D000431:Ethanol; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D013482:Superoxide Dismutase