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Prevention of Doxorubicin-induced Hematotoxicity in Mice by Interleukin 1

Institutes of Cancer and Developmental Biology, Bio-Organic Chemistry [D. A. E., C. G. K., N. A. B.], and Toxicologic Sciences [T. G. T.], Syntex Research, Palo Alto, California 94304

Interleukin 1 and interleukin 1ß induce peripheral neutrophilia with stimulation of granulopoiesis in bone marrow. The continuous administration of interleukin 1 (100 ng/day) to mice for 7 days by s.c.-implanted Alzet osmotic minipumps induced marked stimulation of granulopoiesis in marrow and spleen in normal mice, and protected against the marked depletion of myeloid and erythroid cells in bone marrow of mice treated with single injections of either 20 or 30 mg/kg doxorubicin (DXN). Interleukin 1ß infusion also protected against DXN-induced atrophy of thymus and secondary lymphoid organs. Single i.p. injection of either interleukin 1 or interleukin 1ß at doses up to 1000 ng 24 h prior to treatment with DXN did not protect against the hematopoietic and lymphoid toxicities of DXN.

¹ To whom requests for reprints should be addressed, at Syntex Corporation, 3401 Hillview Avenue, Palo Alto, CA 94303.

Received 10/19/88. Revised 3/15/89. Accepted 4/12/89.