| Objective:To study the effects of recombinant human interleukin-11 (rhIL-11) on peripheral blood stem/progenitor cell mobilization in C57BL/6 mice.Methods:Sixty-four C57BL/6 mice were divided into four groups at random (n=16 each):From day 1 to 7,mice were treated with rhIL-11 250ug .kg.d-1 (Group B),rhG-CSF 250ug .kg-1.d-1 (Group C) and rhIL-11 250ug .kg.d'1 plus rhG-CSF 250ug .kg.d-1 (Group D) respectively,normal control (Group A) with equivalence Saline. Another forty-eight C57BL/6 mice were randomly divided into four groups (n=12 each):normal control (Group E),Cyclophosphamide (CTX) (Group F),CTX + rhIL-11 ( Group G) and CTX + rhIL-11 + rhG-CSF(Group H). CTX 200mg/kg was intraperitoneal injection a day before treatment (dO),rhIL-11 alone or combination with rhG-CSF was injected subcutaneously from dl to d!5. The changes of peripheral blood white cell(WBC) counts,platelet(Plt) counts,the numbers of CFU-GM,CFU-MK,CFU-E,the percent of CD34+,CD3+,CD4+,CD8+ and CD22+ cells of the mice were observed.Results:At day 7,the peripheral WBC counts and Pits counts in group B were great higher than those in group A (P<0.003,0.001 respectively) . The peak value of WBC counts was got in group C and D at day 5 and was higher than that in group A significantly (P=0.001). At the same time,statistic difference of WBC counts existed between group C and D (P=0.04). The numbers of Pit were increased about 30% in group B and D than in group A and C at day 7(P=0.001). At the day 5 and 7,the numbers of CFU-GM,CFU-MK,CFU-E of peripheral blood increased in group B,C and D,and were higher than those in group A. Compared with the control,the number of CFU-GM,CFU-MK,CFU-E in group C,and the numbers of CFU-GM,CFU-E in group D was significantly increased at day 5 (P<0.05). The number of CFU-MK in group B and D were significantly increased than in group A and C at day 7 (P<0.002).The mean of CD34+ cells in the peripheral blood of normal mice was 0.16%-0.2%. After treatment,the CD34+ cells in group B got a percentage of 0.98% and 1.74% at day 5 and 7 respectively. The peak value of 5.4% gotin group D at day 5 is higher than that in group A significantly (P=0.001).The proportion of CD3+ cells in the peripheral blood increased in group B,C and D. In group B,the proportion decreased gradually after day 3;but in group C and D,it increased gradually to normal level. The value of CD4+/CD8+ range from 2.63-2.77 in normal control. After its significant decrease in group B and D,with the increase of CD3+,the value of CD4+/CD8+ increased gradually to normal level.Anti-CD22 expressed on the normal peripheral WBC in mice was about 18.18% - 19.35%. Compared with the control,the proportion of the peripheral blood CD22+ cells were increased significantly in group B,C and D (P<0.05).The nadirs of the peripheral WBC were reached at day 3,but the group H had a higher WBC nadir than in group F or G. Compared with group F,the nadirs of Pit count were significantly improved in group G and H(P<0.003).Semi-solid culture of peripheral blood cell showed that rhIL-11 could stimulate myelosuppressed mice peripheral blood cell to form more CFU-GM,CFU-E,especially CFU-MK.At day 7 and day 9,the percentage of CD34+ cells is 0.34% and 0.4% in group F,0.51% and 0.81% in group G;The percentage of CD34+ cells in group H are 1.52 and 3.0% at day7 and day9,which are higher than that in group E and F.(P<0.05).Conclusion:1. In normal mice,rhIL-11 significantly increased peripheral blood WBC and Pit counts,accelerated reconstitution to normal range of peripheral blood WBC and Pit counts in myelosuppressed mice by CTX.2. rhIL-11 could mobilize stem/progenitor cells from bone marrow to peripheral blood,and stimulate spleen and peripheral blood cell to form more CFU-MK,CFU-GM,CFU-E,especially CFU-MK in C57BL/6 mice.3. The percentage of CD34+ cells and the numbers of CFU-GM,CFU-E and CFU-MK were higher significantly when mobilized by rhIL-11 plus rhG-CSF than rhIL-11 or rhG-CSF alone,which indicate that synergic effect exist between them.4. |
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