Paradoxical effects of cyclosporin A on collagen arthritis in rats.

Abstract

The effect of the immunosuppressive agent cyclosporin A (CS-A) on collagen arthritis in Sprague-Dawley rats is investigated. A 14-day course of CS-A treatment at doses of 15 mg/kg per day or more, begun on the same day as type II collagen immunization, suppressed the development of arthritis as well as humoral and delayed-type hypersensitivty (DTH) skin test responses to type II collagen, possibly by interfering with helper T cells. Additional studies showed that CS-A treatment only during the induction phase of immunity proved to be successful. When CS-A treatment was started only during the immediately preclinical phase of arthritis or after the disease onset, a significant enhancement of the disease was obtained in a dose-dependent manner. This enhancement was accompanied by an augmentation of DTH skin reactions, while antibody responses were either suppressed or unaffected. A suppressive effect of CS-A on a population of suppressor T cells, thus resulting in a T cell-mediated helper effect was suggested. The paradoxical effects of CS-A on collagen arthritis in rats might be caused by an altering of the sensitive balance of the 2 regulatory subpopulations of T cells. Cell-mediated immune responses may play an important role in influencing the course of the disease.