EFFECT OF RECOMBINANT HUMAN INTERLEUKIN-11 ON RAT MEGAKARYOPOIESIS AND THROMBOPOIESIS INVIVO - COMPARATIVE-STUDY WITH INTERLEUKIN-6

The ability of recombinant human interleukin-11 (IL-11) to stimulate rat megakaryopoiesis and thrombopoiesis in vivo was investigated. Once daily subcutaneous injections of IL-11 at doses of 2, 8 and 20 mug/rat for 5 d caused dose-dependent increases in platelet counts. The chronic administration of 20 mug/rat/d for 14 d resulted in biphasic increases in platelet counts with peaks at days 8 and 15 of up to 30% over the control, continuing for more than 5 d after cessation of IL-11 injections. Moreover, a striking increase in megakaryocytic size and ploidy in bone marrow in response to IL-11 was elicited. IL-11 induced a dose-dependent elevation in bone marrow cell numbers but not in splenic weight and cell numbers. Modifications of these parameters were noted as soon as 24 h after the first IL-11 injections. IL-11 had a same potency of thrombopoietic effect in rats as compared with IL-6. However, elevation of acute phase protein such as immunosuppressive acidic protein was 2.2-fold in rats given 20 mug/d of IL-6 over those receiving a same dose of IL-11 (470 v 210 mug/ml). In addition, the rate of body-weight increase in rats receiving IL-11 for 5 d as well as 14 d did not differ from that in control animals. In IL-6 treated rats. the increase in body weight was significantly slower than the controls, which was observed even in the group given 8 mug/d of IL-6. These results suggest that IL-11 may be an effective strategy for the treatment of thrombocytopenia.