Abstract
Rat adjuvant arthritis (AA) was used as a model to evaluate several blood markers as possible predictive indicators of drug efficacy. AA was induced in Sprague-Dawley rats by the injection of complete Freund's adjuvant into the right hind foot pad. The rats were dosed p.o. from day 18 to day 31 with levamisole (10 mg/kg), indomethacin (1 mg/kg), diclofenac sodium (0.5 & 1 mg/kg), and prinomide (10 & 20 mg/kg). Disease severity was assessed by paw circumference on day 31. The following blood markers were analyzed: hyaluronate by ELISA, prostaglandin E2 by RIA, ESR by micro-dispette, total PMN by Technicon H-1, and albumin by BCG dye. Blood marker correlation (r) to disease severity was: hyaluronate (0.71), prostaglandin E2 (0.58), ESR (0.52), PMN (0.58), and albumin (−0.71). The relative rank order of drug efficacy (indomethacin, diclofenac sodium, and prinomide) did not differ using the change in paw circumference (day 31–day 17) or blood markers. Levamisole exacerbated the disease as measured by all the above parameters. Thus, these blood markers provide additional information for the statistical evaluation of drugs in rat adjuvant arthritis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
W. van Eden, J. Holoshitz and I. Cohen,Antigenic mimicry between mycobacteria and cartilage proteoglycans: The model of adjuvant arthritis. InConcepts Immunopathol., (Eds. J. M. Cruse and R. E. Lewis, Jr.) pp. 144–170, Karger, Basel (1987).
M. W. Whitehouse,Adjuvant-induced polyarthritis in rats. CRC-Handbook of animal models for the rheumatic diseases. Vol I. (Eds. R. A. Greenwald and H. S. Diamond) Fl. 3–16 CRC press, (1988).
S. C. Gilman, R. P. Carlson, J. F. Daniels, L. Datko, P. R. Berner, J. Chang and A. J. Lewis,Immunological abnormalities in rats with adjuvant-induced arthritis-II. Effect of antiarthritic therapy on immune function in relation to disease development. Int. J. Immunopharmac.9, 9–16 (1987).
R. L. Goldberg,Enzyme-linked immunosorbent assay for hyaluronate using cartilage proteoglycan and an antibody to keratan sulfate. Anal. Biochem.174, 448–458 (1988).
E. M. O'Byrne, V. J. Blancuzzi, D. E. Wilson, M. Wong, J. Peppard, J. P. Simke and A. Y. Jeng,Increased intra-articular substance P and prostaglandin E 2 following injection of interleukin-1 in rabbits. Int. J. Tissue React.XII, 11–14 (1990).
W. A. Baumgartner, F. W. J. Beck, A. Lorber, C. M. Pearson, and M. W. Whitehouse,Adjuvant disease in rats: Biochemical criteria for distinguishing several phases of inflammation and arthritis (37863). Proc. Soc. Exp. Bio. and Med.145, 625–630 (1974).
R. L. Goldberg and A. S. Rubin,Serum Hyaluronate as a marker for disease severity in the lactobacillus casei model of arthritis in the rat. J. Rheumatol16, 92–96 (1989).
J. J. Cush, P. E. Lipsky, A. E. Postlethwaite, R. E. Schrohenloher, A. Saway, and W. J. Koopman,Correlation of serologic indicators of inflammation with effectiveness of nonsteroidal antiinflammatory drug therapy in rheumatoid arthritis. Arth. Rheum.33, (1990)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Doughty, J.R., Goldberg, R.L., Schenkelaars, E.J. et al. Relationship of blood markers to disease severity and drug efficacy in rat adjuvant arthritis. Agents and Actions 34, 129–131 (1991). https://doi.org/10.1007/BF01993257
Issue Date:
DOI: https://doi.org/10.1007/BF01993257