SEQUENTIAL ANALYSES OF THE DEVELOPMENT OF LYMPHOPROLIFERATIVE DISORDERS IN RATS RECEIVING CYCLOSPORINE

Abstract

Cyclosporine (Cys)-associated, atypical lymphoproliferation in gut-associated lymphoid tissue (GALT) was reproducibly observed in male Sprague Dawley rats by feeding a diet containing 0.015% Cys. Sequential morphological changes occurring in the lymphoid organs of the rats on a Cys diet for 8-10 wk were examined, and these changes were correlated with those observed in electrophoretic patterns of serum proteins. Proliferative lymphoid alterations were detected in the GALT after 2 wk of feeding, and these progressed through 8 wk. Atypical lymphoid proliferation was also seen in lymph nodes after 8 wk of feeding; thymuses showed marked medullary atrophy, and spleens had a diminution of their periarterial lymphoid sheaths. Elevated levels of .gamma.-globulin were detected after 4 wk of Cys administration, and became more pronounced by 8 wk. The lymphoid lesions induced in rats bear striking similarities to the post transplant lymphoproliferative lesions in patients receiving Cys and in patients with the acquired immune deficiency syndrome.