Thrombopoietic activity of recombinant human interleukin-11 in nonhuman primates with ACNU-induced thrombocytopenia.
The effect of recombinant human interleukin-11 (rHuIL-11) on myelosuppressive nimustine (ACNU)-induced thrombocytopenia was assessed in nonhuman primates. A single intravenous (i.v.) injection of ACNU (15 mg/kg) was administered to cynomolgus monkeys on day 0. rHuIL-11 (100 microg/kg/day) or the vehicle was given subcutaneously (s.c.) from day 1 to day 21. In monkeys receiving ACNU, the circulating platelet count decreased to a low of 42 +/- 6 x 10(9)/L by day 21 but returned to pretreatment levels (375 +/- 48 x 10(9)/L) on day 30. Administration of rHuIL-11 prevented severe thrombocytopenia; the platelet count fell only to 138 +/- 23 x 10(9)/L on day 18, and platelet recovery was faster (458 +/- 91 x 10(9)/L by day 27) compared with that of the control animals. The size of bone marrow megakaryocytes from rHuIL-11-treated animals was larger than that of the controls, indicating that rHuIL-11 stimulated megakaryopoiesis in a myelosuppressive condition. Treatment with ACNU also caused leukopenia and moderate anemia. rHuIL-11 transiently and slightly decreased the white blood cell (WBC) and red blood cell (RBC) counts. Conversely, rHuIL-11 accelerated recovery of RBC count in the late administration period. These results support the assertion that rHuIL-11 may be an important therapeutic agent for reducing the severity and duration of thrombocytopenia following cancer chemotherapy.
Saitoh
M
M
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Tsukuba, Ibaraki Prefecture, Japan. saitoh_m@yamanouchi.co.jp
Taguchi
K
K
Yasuda
S
S
Kikumori
M
M
Nishimori
T
T
Suda
M
M
Okamiya
H
H
Usuda
S
S
Miyata
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D004906:Erythrocyte Count; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D007958:Leukocyte Count; D008252:Macaca fascicularis; D008297:Male; D015376:Nimustine / Q000633:toxicity*; D010976:Platelet Count; D011994:Recombinant Proteins / Q000494:pharmacology; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*
D000970:Antineoplastic Agents; D017370:Interleukin-11; D011994:Recombinant Proteins; D015376:Nimustine