Regression of bone and cartilage loss in adjuvant arthritic rats after treatment with cyclosporin A.
To test the effect of cyclosporin A (CsA) on arthritis-related bone resorption, we studied 30 female rats with adjuvant-induced arthritis (AIA). The animals were randomly assigned to 5 groups of 6 animals each; they received daily oral doses of 3, 5, 10, or 15 mg/kg CsA or placebo for 10 days. The parameters studied were (a) caliper measurements of hindpaw swelling, (b) radiometric densitometry of caudal vertebrae, (c) quantitative histomorphometry of radiographed vertebrae, and (d) glycosaminoglycan measurements in femoral condyles. A significant dose-dependent regression of articular swelling occurred in rats given 5, 10, and 15 mg/kg CsA, and this was concomitant with improvement in bone density. These results correlated with those of quantitative bone morphometry. Thus, trabecular volume was significantly reduced in AIA rats, but restoration to virtually normal values occurred with CsA doses between 5 and 15 mg/kg. The protective effect of CsA on articular damage was supported by the dose-dependent progressive improvement in total femoral condyle glycosaminoglycan content. The favorable effect of CsA on AIA is likely due to a blockade of T cell activation via an inhibition of production of lymphokines such as interleukin-2 and gamma-interferon. The consequent cessation of the immune reaction would lead to a reduction in the release of cytokines, such as interleukin-1, that are likely to be the mediators of the pathologic bone and cartilage breakdown that is characteristic of arthritic disease.
del Pozo
E
E
Sandoz Research Institute Berne Ltd., Switzerland.
Graeber
M
M
Elford
P
P
Payne
T
T
D000818:Animals; D001168:Arthritis / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology*; D003524:Cyclosporins / Q000627:therapeutic use*; D003720:Densitometry; D005260:Female; D006025:Glycosaminoglycans / Q000032:analysis; D007375:Interleukin-1 / Q000096:biosynthesis; D008222:Lymphokines / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology
D003524:Cyclosporins; D006025:Glycosaminoglycans; D007375:Interleukin-1; D008222:Lymphokines