The effect of the immunosuppressive agent FK-506 (FK) on collagen arthritis in Sprague-Dawley rats is investigated. A 14-d course of FK treatment at a dose of 1.0mg/kg per day, begun on the same day as type 11 collagen immunization, suppressed completely the development of a arthritis as well as humoral and delayed-type hyper-sensitivity (DTH) skin test response to type 11 collagen. To study whether the immunologic unresponsiveness can be produced by FK, we rechallenged the FK-protected rats with type 11 collagen after discontinuation of FK treatment. Type 11 collagenimmunized, FK-protected rats did not develop arthritis in response to reimmunized with type 11 collagen.
Furthermore, to study whether FK-mediated unresponsiveness can be transeferred passively with serum, we immunized with type 11 collagen the naive recipient rats, which were transferred with the serum from FK-treated, type 11 collagen tolerant donor rats on the same day of immunization. Serum-transferred recipient rats showed a suppressed arthritogenic reaction in response to immunization with type 11 collagen.
These results indicate that immunologic unresponsiveness can be induced by FK in the experimental model of polyarthritis, collagen arthritis, and that its unresponsiveness can be transferred passively with serum. The results further indicate that humoral properties may, at rest in part, participate in the immunosuppressive mechanism of FK nad the regulation of the clinical course in the experimental model of polyarthritis in rats.
