A toxicological study in rats receiving immunotherapeutic doses of cyclosporin A.

Cyclosporin A (Cy A, 25 or 50 mg.kg-1/48 hr) administered during the course of the response, markedly suppressed graft-versus-host (GVH) reactivity in the rat, as assessed by the 7-day popliteal lymph node weight assay. Serum biochemical studies revealed small, but statistically significant increases in serum urea levels at both doses of Cy A and, at 50 mg.kg-1/48 hr, reduction in total serum protein, alkaline phosphatase, serum transaminase, and iron. In an additional experiment, Cy A (50 mg.kg-1/48 hr) was administered to rats over 4 weeks. Serum biochemical and hematological investigations were conducted at weekly intervals and at 28 days tissue (liver, kidney, spleen, lymph nodes, and small intestine) was taken for histological and ultrastructural examination. Glomerular function, monitored by creatinine and urea clearance was unaffected by Cy A treatment, but serum urea and creatinine levels were elevated. Hepatic function was not affected and hematological, histological, and ultrastructural observations, apart from evidence of hepatic fatty change, did not differ from those in vehicle-treated controls.