Paradoxical effects of cyclosporin A on collagen arthritis in rats

The effect of the immunosuppressive agent cyclosporin A (CS-A) on collagen arthritis in Sprague-Dawley rats is investigated. A 14-d 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 hypersensitivity (DTH) skin test responses to type II collagen, possibly by interfering with helper T cells. Additional studies demonstrated 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. These results appear to be attributable at least in part to a suppressive effect of CS-A on a population of suppressor T cells, thus resulting in a T cell-mediated helper effect. It is therefore reasonable to assume that the paradoxical effects of CS-A on collagen arthritis in rats might be caused by an altering of the sensitive balance of the two regulatory subpopulations of T cells. It is also possible that cell-mediated immune responses may play an important role in influencing the course of the disease.