Effect of recombinant human interleukin-11 on rat megakaryopoiesis and thrombopoiesis in vivo: 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 micrograms/rat for 5 d caused dose-dependent increases in platelet counts. The chronic administration of 20 micrograms/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 micrograms/d of IL-6 over those receiving a same dose of IL-11 (470 v 210 micrograms/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 micrograms/d of IL-6. These results suggest that IL-11 may be an effective strategy for the treatment of thrombocytopenia.
Yonemura
Y
Y
Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Kawakita
M
M
Masuda
T
T
Fujimoto
K
K
Takatsuki
K
K
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology*; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D008533:Megakaryocytes / Q000166:cytology; D010976:Platelet Count / Q000187:drug effects; D011003:Ploidies; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology
D017370:Interleukin-11; D015850:Interleukin-6; D011994:Recombinant Proteins