BACKGROUND: The megakaryopoiesis and platelet production is regulated by several hematopoietc factors such as thrombopoietin (TPO), interleukin-11 (IL-11) and interleukin-3 (IL-3). IL-11 is a potent stimulator of megakaryopoiesis in vivo, and acts primarily as a megakaryocyte maturation factor in vitro and it can act synergistically with IL-3 and TPO. We performed this study to investigate the effects of recombinant human IL-11 (rhIL-11) with other hematopoietic factors on megakaryocyte colony formation in vitro. METHODS: CD34+ cells were separated from umbilical cord blood and megakaryocyte colonies using MegaCult Assay Kit were cultured with rhIL-11, recombinant human IL-3 (rhIL-3), and recombinant human TPO (rhTPO) for 7 and 14 days. The number and percentage of CD34+ and CD41a+ cells were determined by flowcytometry. RESULTS: The number of CD41a+ cells were 0.54+/-0.05x10(4) (rhIL-11 100 ng/ml), 5.32+.-0.23x10(4) (rhIL-3 100 ng/ml), and 8.76+/-0.15x10(4) (rhTPO 50 ng/ml) of total expanded cells during the culture of the purified CD34+ cells in liquid phase for 7 days. The number of CD41a+ cells were increased to 7.47+/-0.69x10(4) (rhIL-3 rhIL-11), 11.92+/-0.19x10(4) (rhTPO rhIL-11) of total expanded cells, respectively, during the culture of the purified CD34+ cells in liquid phase for 7 days in the presence of rhIL-11 (100 ng/ml). When the purified CD34+ cells were cultured in semisolid media including various concentration of rhIL-11, the megakaryocyte colonies were not formed. When the purified CD34+ cells were cultured with rhIL-11 and rhTPO or with rhIL-11 and rhIL-3, the number of megakaryocyte colonies were increased compared with rhTPO or rhIL-3 alone. CONCLUSION: These results indicate that IL-11 exerts a potent proliferative activity to colony forming unit-megakaryocyte from human umbilical cord blood, and it acts with other hematopoietic factors synergistically
Blood Platelets ; Fetal Blood* ; Humans ; Interleukin-11* ; Interleukin-3 ; Megakaryocytes ; Thrombopoietin ; Umbilical Cord*

PURPOSE: The platelet synthesis is extremely variable after intravenous immunoglogulin injection (IVIG) in acute idiopathic thrombocytopenic purpura (ITP). To investigate the size variation of platelet according to the time sequence of ITP, the relationship between platelet number and mean platelet volume (MPV) was analyzed. METHODS: Twenty acute ITP patients who showed abrupt increase of platelets within 48 hours after IVIG were selected. We checked the platelet number and MPV, thereafter analyzed the relationship. RESULTS: At the early phase of ITP before IVIG, MPV was normal or slightly decreased. However, as the number of platelet increased after IVIG, MPV increased together until platelet count reached 100, 000/mm3. The MPV decreased afterward, therefore the platelet mass was preserved. CONCLUSION: At the early phase of ITP before the increase of platelet, MPV decreased in spite of low number of platelet. After IVIG, there was an abrupt increase of MPV with platelet number. There might be some contributing factors for these, particularly IL-6, IL-11 and thrombopoietin. Now, we need more experimental data to explain these findings.
Blood Platelets* ; Humans ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Interleukin-11 ; Interleukin-6 ; Mean Platelet Volume* ; Platelet Count* ; Purpura, Thrombocytopenic, Idiopathic* ; Thrombopoietin

Animals ; Blood Coagulation ; drug effects ; Blood Platelets ; drug effects ; Female ; Haplorhini ; Humans ; Interleukin-11 ; pharmacology ; Male ; Platelet Count ; Thrombopoietin ; pharmacology

In order to investigate the influence of cytokine combinations on proliferation and differentiation of human umbilical cord blood CD34(+) cells into megakaryocytes/platelets in vitro, the CD34(+) cells from human umbilical cord blood were amplified in serum-free medium StemSpan(SFEM) supplemented with several cytokine combinations by three-phase culture system. The effects of the cytokine combinations were compared. The results showed that at day 14 of the first culture phase, the CD34(+) cells cultured with cytokine combinations SCF + TPO + FL + IL-3 were amplified (11 000 ± 1 000) times, which were significantly higher than that of cells cultured with SCF + TPO + FL, but were not significantly different from that of cells cultured with SCF + TPO + IL-3 or SCF + TPO + FL + IL-3+ hydroxyl-corticosteroids. At day 7 of the second culture phase, the CD34(+) cells cultured with cytokine combination SCF + TPO + FL + IL-11 were amplified by (204666.7 ± 11718.9) times, which were significantly higher than that of cells cultured with SCF + TPO + FL + IL-3, but were not significantly different from that of cells cultured with SCF + TPO + FL + IL-11 + BMP4 + VEGF. At day 3 and day 6, the CD34(+) platelet-like cells accounted for about (39.8 ± 1.9)%, (39.7 ± 2.6)% and (25.5 ± 1.4)%, (23.1 ± 3.5)% cultured with SCF + TPO + FL + IL-11 and SCF + TPO + FL + IL-11 + BMP4 + VEGF, and significantly higher than that of the cells cultured with SCF + TPO + FL + IL-3. It is concluded that the cytokine combination of SCF + TPO + FL + IL-3 is most suitable cytokines combination for the amplification of CD34(+) hematopoietic progenitor cells. The cytokine combination of SCF + TPO + FL + IL-11 is preferred for the proliferation and differentiation of megakaryocytes, this study lays an experimental basis for investigating the proliferation and differentiation of CD34(+) into megakaryocytes/platelets in vitro.
Antigens, CD34 ; immunology ; Blood Platelets ; cytology ; Cell Differentiation ; Fetal Blood ; cytology ; immunology ; Humans ; Interleukin-11 ; pharmacology ; Interleukin-3 ; pharmacology ; Megakaryocytes ; cytology ; Stem Cell Factor ; pharmacology ; Thrombopoietin ; pharmacology

PURPOSE: This study was performed to determine whether the serum concentrations of interleukin (IL)-6 family cytokines are elevated in patients with rheumatoid arthritis (RA) and to investigate the relationship between IL-6 family cytokine levels and disease activity in RA patients. MATERIALS AND METHODS: We obtained serum samples from 40 patients with RA and 40 age- and sex-matched healthy controls, and we assessed the clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP) levels. Serum samples from five patients with high disease activity (DAS28 > 5.1) were also collected at the eighth week of treatment. Serum concentrations of IL-6, IL-11, and leukemia inhibitory factor (LIF) were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum concentrations of IL-6 family cytokines, including IL-6, IL-11, and LIF, were significantly elevated in patients with RA compared to those of healthy controls. Although there was no significant relationship between IL-6 family cytokine levels and DAS28, the IL-6 levels of patients with RA showed a significant correlation with CRP levels. After eight weeks of medical treatment in patients with high disease activity, a decrease in DAS28 was associated with a significant decrease in the serum concentrations of IL-6 and IL-11. CONCLUSION: The serum concentrations of IL-6 family cytokines were significantly elevated in patients with RA, and they decreased with medical treatment. These findings suggest a possible role for IL-6 family cytokines in the pathogenesis of RA.
Adult ; Aged ; Aged, 80 and over ; Arthritis, Rheumatoid/*blood ; C-Reactive Protein/analysis ; Cytokines/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-11/blood ; Interleukin-6/*blood ; Leukemia Inhibitory Factor/blood ; Male ; Middle Aged ; Young Adult

In order to evaluated the curative effect of rhIL-11 (Mega) on thrombocytopenia in chronic aplastic anemia (CAA) patients, ten CAA cases with thrombocytopenia after administration of conventional drugs were selected and subcutaneously injected 0.75 mg Mega per day in 1 - 2 courses of treatment on the basis of conventional therapy. Results showed that platelet counts were obviously increased and the bleeding symptoms were alleviated in all CAA patients after application of Mega for treatment. In conclusion, the rhIL-11 (Mega) could be used as an effective drug for treatment of thrombocytopenia in CAA patients.
Adolescent ; Adult ; Anemia, Aplastic ; blood ; therapy ; Chronic Disease ; Female ; Humans ; Interleukin-11 ; therapeutic use ; Male ; Middle Aged ; Platelet Count ; Recombinant Proteins ; therapeutic use ; Thrombocytopenia ; blood ; therapy

The aim of this study was to investigate the circulating levels of IL-11 in the patients with chronic idiopathic thrombocytopenic purpura (CITP), and its significance, and to evaluate the curative effect of rhIL-11 on CITP. The level of IL-11 in patients with CITP was determined by ELISA before and after treatment, respectively. 1.5 mg of rhIL-11 were injected subcutaneously, once a day, continuously for 14 days as one course, treatment time 1 - 2 courses as total. The results showed that the higher blood IL-11 level was found in CITP patients than that in controls (P < 0.01) and during the course of treatment the number of platelets in peripheral blood of patients with CITP parallelled to the level of IL-11. The platelet counts were obviously increased in all CITP patients after rhIL-11 treatment. It is concluded that the serum level of IL-11 in patients is correlated to the number of platelets in patients. rhIL-11 can be used as an effective treatment for CITP.
Adolescent ; Adult ; Aged ; Chronic Disease ; Female ; Humans ; Interleukin-11 ; blood ; therapeutic use ; Male ; Middle Aged ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Recombinant Proteins ; therapeutic use ; Treatment Outcome

OBJECTIVETo observe whether rhIL-11 could accelerate the engraftment of platelets after unrelated cord blood transplantation (CBT).

METHODSNine patients (3 children and 6 adults) were enrolled in this study. The degree of HLA disparity was 0-2 loci. Cord blood was given two units for adults and one unit for children. Conditioning regimens were CY/TBI in 1 and BU/CY in 8 cases, both with antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-term methotrexate. On day +1, rhIL-11 was used at 50 microg x kg(-1) x d(-1) and G-CSF at 5 microg x kg(-1) x d(-1) to accelerate hematopoiesis recovery.

RESULTSThe median age of the patients was 22.3 years and the median weight 52.3 kg. Among the 9 patients, 8 (88.9%) experienced engraftment. The median time to neutrophil > 0.5 x 10(9)/L was 21.3 (14-37) days and to platelet > 20 x 10(9)/L was 25 (18-36) days. 42.9% of the patients developed grade I aGVHD and 33.3% developed localized chronic GVHD. Six patients were alive and disease-free at a median follow-up of 7 months. Infection was the primary cause of death. The expected 1-year survival was 77.8%, 2-year survival was 52.2%. Five of 8 patients (62.5%) who received IL-11 presented leakage syndrome. On prophylaxis with drugs containing Arnebia root extract, all patients could tolerate the treatment.

CONCLUSIONrhIL-11 maybe helpful for accelerating the platelet recovery and reducing aGVHD severity in unrelated CBT. The major side effect is leakage syndrome. It is well tolerated on prophylaxis with drugs containing Arnebia root.

Adolescent ; Adult ; Blood Platelets ; drug effects ; Child ; Cord Blood Stem Cell Transplantation ; Female ; Follow-Up Studies ; Graft vs Host Disease ; prevention & control ; Humans ; Interleukin-11 ; pharmacology ; Male ; Recombinant Proteins ; pharmacology

The aim of this study was to explore the effect of recombinant human interleukin 11 (rhIL-11) on platelet recovery after peripheral blood hematopoietic stem cell transplantation and its side-effects. 20 patients with hematologic malignancies treated by allogeneic peripheral blood stem cell transplantation (PBSCT) were randomly divided into test and control groups. The patients in test group were treated with rhIL-11 since the day 6 after PBSCT, while the patients in control group were given supporting treatment. The results showed that the average time of the platelet to recover to 20 x 10(9)/L was 22.8 days in test group and 27.3 days in control group (p < 0.01). The average time for platelet to recover to 50 x 10(9)/L was 25.7 days in test group, and 32.3 days in control group (p < 0.01). The average number of megakaryocytes was 15.6 in test group, and 7.8 in control group on day 30 after PBSCT (p < 0.01). In conclusion, the rhIL-11 is able to accelerate platelet recovery after peripheral blood hematopoietic stem cell transplantation.
Adolescent ; Adult ; Blood Platelets ; drug effects ; Female ; Humans ; Interleukin-11 ; therapeutic use ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; methods ; Platelet Count ; Recombinant Proteins ; therapeutic use ; Young Adult

OBJECTIVETo evaluate the efficacy and toxicity of domestic recombinant human interleukin-11 (rhIL-11) in the prevention of chemotherapy-induced thrombocytopenia.

METHODSA randomized, self-crossover and placebo-controlled trial was conducted, with rhIL-11 and placebo classified randomly as drug A and drug B. Patients were randomly assigned to group AB or group BA. 25 microg/kg body weight of drug A or drug B was administered subcutaneously once daily starting 24 hours after chemotherapy and continued for 7 to 14 days or until the platelet count reached > or = 300 x 10(9)/L.

RESULTS118 patients were evaluable in the efficacy study. When compared with the placebo treated cycle, the results showed that rhIL-11 was able to significantly increase the platelet count at the nadir and d21 after chemotherapy, with a increase of 60.7% and 86.1% (both P < 0.001). The mean duration of thrombocytopenia (< 100 x 10(9)/L) in rhIL-11 treated cycle was 1.0 +/- 2.0 days as compared to 6.9 +/- 5.3 days in placebo treated cycle. The side effects were ache (24.6%), swelling (16.1%) and knurl (11.9%) at the injection site, hyperaemia of conjunctiva (16.1%), edema (8.5%), palpitation (6.8%) and fatigue (5.1%).

CONCLUSIONrhIL-11, possessing significant thrompoietic activity, significantly increases the likelihood of avoiding chemotherapy-induced thrombocytopenia and shorten the duration of thrombocytopenia. Its side effects are mild and manageable.

Adolescent ; Adult ; Aged ; Antineoplastic Agents ; adverse effects ; Cross-Over Studies ; Double-Blind Method ; Humans ; Interleukin-11 ; adverse effects ; therapeutic use ; Middle Aged ; Neoplasms ; blood ; drug therapy ; Recombinant Proteins ; therapeutic use ; Thrombocytopenia ; prevention & control