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 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

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

This study was aimed to evaluate the effects of recombinant human interleukin 11 (rhIL-11) and recombinant human granulocyte colony stimulating factor (rhG-CSF) in mobilization for autologous peripheral blood stem cell transplantation (APBSCT). 16 patients with non-Hodgkin's lymphoma or acute myeloblastic leukemia were given myelosuppressive chemotherapy, then were mobilized by using rhG-CSF 5 microg/(kg.d) for median 5.5 days and rhIL-11 50 microg/(kg.d) for median 4 days (experimental group) or rhG-CSF 5 microg/(kg.d) alone for median 5.5 days (control group). After mobilizing, the peripheral blood leucocyte and platelet counts, total mononuclear cells, CD34+ cells and CFU-GM counts in PBSC collection, and amount of apheresed platelet transfusion were assayed. The results showed that the peripheral blood leucocyte and platelet counts, total mononuclear cell, CD34+ cell and CFU-GM counts in PBSC collection were no significant difference between two groups (p>0.05). After APBSCT, the median time for neutrophil count>or=0.5x10(9)/L and the median time for platelet count>or=20x10(9)/L were 10.5 and 11.5 days in experimental group, while were 13 and 13 days in control group, respectively. The median amount of apheresed platelet transfusion was 3.5 unit in experimental group and 5 unit in control group. Data were significantly different between two groups (p<0.05). The adverse reactions of mobilization were mild fever, fatigue, symptoms like as common cold, poor appetite, dizziness, muscular soreness in experimental group, but only mild fever in control. These symptoms were well tolerated and overcome with drug withdrawal. It is concluded that the regimen of rhIL-11 in combination with rhG-CSF after myelosuppressive chemotherapy to mobilize PBSC is efficient and safe with rapid hematologic reconstitution and less platelet transfusions after APBSCT were used.
Adolescent ; Adult ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Hematopoietic Stem Cell Mobilization ; adverse effects ; methods ; Humans ; Interleukin-11 ; administration & dosage ; Leukemia, Myeloid, Acute ; therapy ; Lymphoma, Non-Hodgkin ; therapy ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; methods ; Recombinant Proteins ; Transplantation, Autologous ; Young Adult

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

OBJECTIVE: To explore the effect and toxicity profile of recombinant human interleukin 11(rhIL-11) on the platelet after hematopoietic stem cell transplantation in patients with leukemia. METHODS: Twenty-four patients with acute or chronic leukemia treated by allogeneic peripheral blood stem cell transplantation (PBSCT) were randomly divided into a test group and a control group. The patients in the test group were treated with rhIL-11 since the 13th day after PBSCT (1.5mg/d),while the control group were given symptomatic treatment. RESULTS: The average time for the platelet to recover to the level of 20 x 10(9)/L was 20.8 days in the test group, and 26.0 days in control group respectively, there was significant difference (P<0.01). The average time for the platelet to recover to the level of 50 x 10(9)/L was 25.7 days in the test group, and 32.3 days in the control group respectively, there was also significant difference (P<0.01). The average time for the platelet transfusion was 2.2 in the test group, 4.1 in the control group, and there was significantly different (P<0.01). The average number of megakaryocytes was 12.2 in the test group, 4.8 in the control group on 30th day after the transplantation,and there was significant difference(P<0.01). The main side effects of rhIL-11 were nausea, vomit, debility, headache, dizzy and pain of injection site, and the degree was all Iapproximately II grade. CONCLUSION rhIL-11 has definite recuperative effect on the recovery of the platelet after PBSCT. There is little side effect, and it can be accepted.
Adolescent ; Adult ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Interleukin-11 ; genetics ; therapeutic use ; Leukemia ; blood ; surgery ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; surgery ; Leukemia, Myeloid, Acute ; blood ; surgery ; Male ; Middle Aged ; Platelet Count ; Recombinant Proteins ; therapeutic use ; Thrombocytopenia ; drug therapy ; Treatment Outcome

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 investigate the effectiveness, safety and possible mechanism of recombinate human interleukin 11 (rhIL-11) in the treatment of chemotherapy-induced thrombocytopenia.

METHODSThirty-four patients (totally 76 cycles) with chemotherapy-induced thrombocytopenia received subcutaneous injection of rhIL-11 at the dose of 25 microg.kg(-1).d(-1) for 4 to 16 days. Serum IL-11 level was measured by ELISA, and IL-11 R alpha expression was detected by RT-PCR.

RESULTSThe mean baseline platelet count before chemotherapy was (135.0 +/- 54.3) x 10(9)/L for the 1st cycle and (259.4 +/- 64.5) x 10(9)/L for the 2nd cycle. The time to administer rhIL-11 was 7 to 16 days (median 12 days) in the 1st cycle and 4 to 10 days (median 6 days) in the 2nd, respectively (P < 0.05). The duration of post-chemotherapy platelet count below 50 x 10(9)/L was 7 to 13 days (median 10 days) for the 1st cycle and 3 to 8 days (median 5 days) for the 2nd, respectively (P < 0.05). Platelet count reached 300 x 10(9)/L or above in 30 chemotherapy cycles. The maximum platelet count was found to appear at D10 to D 17 (median D14), and negatively correlated with the pre-chemotherapy serum IL-11 level after administration of rhIL-11. Major adverse reactions included edema, headache, muscle and joint pain.

CONCLUSIONrhIL-11 is effective and safe for the treatment of chemotherapy-induced thrombocytopenia, with a relatively slow but sustained effect on the recovery of platelet count. Pre-chemotherpy serum IL-11 level might predict the efficacy of rhIL-11.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Female ; Humans ; Injections, Subcutaneous ; Interleukin-11 ; administration & dosage ; adverse effects ; blood ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Platelet Count ; Recombinant Proteins ; administration & dosage ; adverse effects ; Thrombocytopenia ; chemically induced ; drug therapy ; Treatment Outcome

OBJECTIVETo expand cord blood megakaryocyte progenitor cells in vitro.

METHODSCord blood CD34+ cells were selected by magnetic cell sorting (MACS), and thrombopoietin (TPO), interleukin-11 (IL-11), and heparin were used in the expansion system of megakaryocyte progenitor. The expansion efficiency was measured by fluorescence-activated cell sorting (FACS) using the megakaryocytic specific monoclonal antibodies (CD34+, CD41a+, CD61+, CD34+CD41a+, CD41a+CD61+) and colony-forming units-megakaryocyte (CFU-MK) analysis. The expanded megakaryocyte progenitor were determined by histochemistry staining using CD41a and the observation of the ultrastructure of megakaryocyte (MK) by electron microscopy. The megakaryocyte function were examined by the platelet activation in vitro and nonobese diabetic/severe combined immunodifficiency (NOD/SCID) mice transplantation in vivo.

RESULTSCD34+CD41a+ cells was expanded (4.0 +/- 1.7) folds on day 7 in TPO (50 ng/ml) group and (10.5 +/- 4.8) fold in TPO combined with IL-11 group; after heparin was joined in on day 0, a more significantly elevated expansion was found in the heparin, TPO, and IL-11 group [(29.9 +/- 6.4) folds than the above two groups; P < 0.05]. Meanwhile, the large CFU-MK colony (> 50 cells/colony) was (106.8 +/- 26.9) folds on day 7 (P < 0.05). The megakaryocyte expanding with TPO, IL-11 and heparin for 7 days in vitro transplanted the NOD/SCID mice fasten the recovery of platelet and white blood cell account and improved the survival. Megakaryocyte under culture displayed certain development of territories membrane. Platelet activation test comfirmed that the expanding megakaryocyte progenitor had the normal function.

CONCLUSIONTPO, IL-11, and heparin combination system for ex vivo expansion is an effective expansion system of megakaryocyte progenitor.

Animals ; Antigens, CD34 ; Cell Differentiation ; drug effects ; immunology ; Cell Division ; drug effects ; Cells, Cultured ; Fetal Blood ; cytology ; Hematopoietic Stem Cells ; cytology ; drug effects ; immunology ; Heparin ; pharmacology ; Humans ; Interleukin-11 ; pharmacology ; Male ; Megakaryocytes ; cytology ; immunology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Thrombopoietin ; pharmacology

To evaluate the clinical efficacy of recombinant human Interleukin 11 in the treatment of pre-aplastic anemia, six patients with pre-aplastic anemia were injected with rhIL-11 of 6 million units once a day during 7-14 days. Blood platelet counts were taken on day 8, 15, 30 and 60 after the treatment, and bone marrow examination was performed on day 15 as compared with those before treatment. The results showed that platelet counts in 3 out of 6 patients increased remarkably (50%), one of the six increased moderately (16.7%), another case of the six increased slightly (16.7%), platelet in one out of six did not significantly increase (16.7%), the total efficacy rate is 83.3%, the amount of megakaryocyte in bone marrow of all six patients increased, the side effect of the rhIL-11 treatment was light. In conclusion, the efficacy of recombinant human Interleukin-11 in the treatment of thrombocytopenia patients with pre-aplastic anemia is satisfactory. As the number of the cases is too small to conclude, further exploration needs accumulation of more applications.
Adult ; Aged ; Anemia, Aplastic ; drug therapy ; pathology ; Chronic Disease ; Female ; Humans ; Interleukin-11 ; genetics ; therapeutic use ; Male ; Middle Aged ; Platelet Count ; Recombinant Proteins ; therapeutic use ; Thrombocytopenia ; blood ; drug therapy ; Treatment Outcome