title: [Thrombocytopoietic Efficacy of Pegylated Recombinant Human Interleukin-11 Mutein in Myelosuppressed Mice].
abstract: OBJECTIVE
  To evaluate the effect of PEGylated IL-11 mutein (PEG-mIL 11) with different dose or injection frequency on thrombocytopenia in myelosuppressed mice and to compare its effect with mIL-11, so as to provide reference data for clinical use.
  
  
  METHODS
  Myelosuppressive model with thrombocyopenia was produced in BALB/c mice by whole body60Co γ-ray irradiation in dose of administration 2.5 Gy followed by i.p. injections of carboplatin at 50 mg/kg. In study of injection frequency, 30 thrombocytopenic BALB/c mice were randomly divided into 5 groups: vehicle control group (once daily on d1, 4, 7), mIL-11 group [200 µg/(kg·d)×9 d], PEG-mIL 11 A group [111800 µg/(kg·d)×1 d (d 1)], PEG-mIL 11 B group 900 µg/(kg·d)×2 d (d 1,5), and PEG-mIL 11 C group [600 µg/(kg·d)×3 d (d 1,4,7)]. The route of administration is subcutaneous injection. The platelet counts were monitored in the subsequant 5 weeks. In study of dose administration, 100 thrombocytopenic BALB/c mice were randomly divided into 5 groups: vehicle control group (once daily on d1 and 5), mIL-11 group 200 µg/(kg·d)×9 d, and PEG-mIL 11 low-, mid-, and high-dose groups (200, 420 and 900 µg/(kg·d)×2 d, once a day on d1 and 5). The route of administration is subcutaneous injection. The platelet counts were monitored every 2-3 days in the subsequant 5 weeks, and CFU-Meg was determined on d 8 of the bone marrow cells collection.
  
  
  RESULTS
  After60Co irradition and carboplatin injection, Plt level decreased with time, and a >80% reduction was noted at nadir when comparing with baseline. In frequency of administration study, the platelet nadir of the 3 PEG-mIL 11 groups were significantly higher than that of vehicle control and mIL-11 groups (P<0.05), while no significant difference was noted among the 3 groups of different administration frequences; In dose level study, the reduction of Plt count at the nadir in the 3 PEG-mIL 11 groups was significantly less than that of vehicle control and mIL-11 groups (P<0.05). And a rapid recovery of Plt count was found in the PEG-mIL 11 groups with a dose-dependent increase of Plt count on d 10. A lower reduction and a rapider recovery of RBC was also found in the PEG-mIL 11 groups. No significant effect on WBC was found for all the treatment groups. An increase in CFU-Meg was observed in PEG-mIL 11 and mIL-11 groups, with higher CFU-Meg in PEG-mIL 11 groups.
  
  
  CONCLUSIONS
  A preventive effect of PEG-mIL 11 on thrombocytopenia in myelosuppressed mice has been confirmed. In comparison with mIL-11, a better effect of PEG-mIL 11 is obtained under lower dose frequency, indicating a better compliance of the treatment regimen, and providing a foundation for developing a long-acting preparation of rhIL-11.
authors: Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; Beijing Northland Biotech. Co., Ltd., Beijing 100085,China.
authors: Shan-Shan
authors: SS
authors: Ma
authors: ViroMed Co., Ltd., Seoul 151-818, Korea.
authors: Seong-Hyun
authors: SH
authors: Ho
authors: Beijing Key Laboratory of Bio-products Safety Assessment, Joinn Laboratories Inc. Beijing 100176, China.
authors: Hong-Ling
authors: HL
authors: Wang
authors: Beijing Northland Biotech. Co., Ltd., Beijing 100085,China.
authors: Li-Ya
authors: LY
authors: Nie
authors: Beijing Northland Biotech. Co., Ltd., Beijing 100085,China. E-mail:xusongshan@northland-bio.com.
authors: Song-Shan
authors: SS
authors: Xu
mesh_terms: D000818:Animals; D001792:Blood Platelets; D001854:Bone Marrow Cells; D016190:Carboplatin; D006801:Humans; D017370:Interleukin-11; D051379:Mice; D008807:Mice, Inbred BALB C; D010976:Platelet Count; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D013921:Thrombocytopenia; D034061:Thrombopoiesis; D013926:Thrombopoietin
chemical_list: C508611:IL11 protein, human; D017370:Interleukin-11; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D013926:Thrombopoietin; D016190:Carboplatin; C105308:oprelvekin