Abstract
The anti-inflammatory activity of the IL-1 receptor antagonist, IL-1ra, was evaluated in the acetic acid (HOAc)-induced model of colitis in rats. Animals treated with 10 mg/kg IL-1ra or vehicle were evaluated for general health, acute phase response, and colonic in flammation 24 hours after the initiation of inflammation. A significant decrease in the accumulation of neutrophils in the colonic mucosa as measured by myeloperoxidase activity was seen in animals with HOAc induced colitis that were treated intraperitoneally with IL-1ra when compared to animals with colitis that had been treated with vehicle. IL-1ra also reduced colonic necrosis measured grossly, although there was no effect on the histology IL-1ra had a modest effect on the HOAc-induced acute phase response, as indicated by changes in the serum iron, albumin and transferrin, but the results were not statistically significant. The number of circulating erythrocytes and neutrophils was significantly increased in animals with HOAc-induced colitis and treated with IL-1ra, suggesting that IL-1ra under these experimental conditions inhibited the migration of neutrophils to the injured colon and also the overall intestinal necrosis in the colon as assessed by gross pathology. IL-1ra may be useful as an intestinal anti-inflammatory agent.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
P. Sharon and W. F. Stetson,Metabolism of arachidonic acid in acetic acid colitis in rats. Similarity to human inflammatory bowel disease. Gastroenterology.88, 55–63 (1985).
J. Satsangi, R. A. Wolstencroft, J. Cason, C. C. Ainley and R. P. H. Thompson,Interleukin 1 in Crohn's disease. Clin. Exp. Immunol.67, 594–605 (1987).
D. Rachmilewitz, P. L. Simon, L. W. Schwartz, D. E. Griswold, J. D. Fondacaro and M. A. Wasserman,Inflammatory mediators of experimental colitis in rats. Gastroenterology.97, 326–337 (1989).
F. Cominelli, C. C. Nast, R. Schindler, B. Clark, R. Llerena, V. E. Eysselein and C. A. Dinarello,Interleukin-1 gene expression and production is an early event in rabbit formalin-immune complex colitis. Gastroenterology.98, A442 (1990).
C. H. Hannum, C. J. Wilcox, W. P. Arend, F. G. Joslin, D. J. Dripps, P. L. Heimdal, L. G. Armes, A. Sommer, S. P. Eisenberg and R. C. Thompson,Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature.343, 336–340 (1990).
J. E. Krawisz, P. Sharon and W. F. Stenson,Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology.87, 1344–1350 (1984).
J. H. Zar,Biostatistical Analysis, pp. 138–144, 185–193, Prentice-Hall, Englewood Cliffs, NJ, 1984.
D. B. Carter, M. R. Deibel, Jr, C. J. Dunn, C. S. C. Tomich, A. L. Laborde, J. L. Slightom, A. A. Berger, M. J. Bienkowski, F. F. Sun, R. N. McEwan, P. W. W. Harris, A. W. Yem, G. A. Waszak, J. G. Chosay, L. C. Sieu, M. M. Hardee, H. A. Zurcher-Neely, I. M. Reardon, R. L. Heinrikson, S. E. Truesdell, J. A. Shelly, T. E. Eessalu, B. M. Taylor and D. E. Tracey,Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein. Nature.344, 633–637 (1990).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Thomas, T.K., Will, P.C., Srivastava, A. et al. Evaluation of an interleukin-1 receptor antagonist in the rat acetic acid-induced colitis model. Agents and Actions 34, 187–190 (1991). https://doi.org/10.1007/BF01993274
Issue Date:
DOI: https://doi.org/10.1007/BF01993274