OBJECTIVES: To investigate the effect of Shenge powder (SGP) on myocardial fibrosis in rats with heart failure after myocardial infarction and its relation with lysyl oxidase like protein 2 (LOXL2)/transforming growth factor-β1 (TGF-β1)/IL-11 signaling pathway. METHODS: Seventy-two SPF male SD rats were divided into blank control group, model control group, SGP small dose group, SGP large dose group, positive control group, SGP large dose+LOXL2 activator group, with 12 rats in each group. Except for the blank control group, post-myocardial infarction heart failure was induced by coronary constriction. Corresponding treatments were given immediately after successful modeling, once a day for 4 weeks. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in rats were detected by color Doppler ultrasound imaging. Levels of IL-1β and IL-6 in serum were analyzed by ELISA method. Myocardial collagen volume fraction (CVF) was evaluated by Masson staining. Expressions of collagen Ⅰ and α-smooth muscle actin (α-SMA) in myocardial tissue were detected by immunohistochemical staining. The mRNA expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in myocardial tissue were detected by qRT-PCR. Expression of LOXL2, TGF-β1, and IL-11 proteins in myocardial tissue were detected by Western blotting. RESULTS: Compared with the blank control group, the LVFS and LVEF of the model control group decreased, the levels of serum IL-6 and IL-1β elevated, and the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, MMP-9 and TIMP-1 mRNA, and LOXL2, TGF-β1, IL-11 proteins increased (all P<0.05). Compared with the model control group, the LVFS and LVEF of SGP small dose group, SGP large dose group and positive control group increased, the levels of serum IL-6 and IL-1β decreased, and the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, MMP-9 and TIMP-1 mRNA, and LOXL2, TGF-β1, IL-11 proteins decreased (all P<0.05); while LOXL2 activator reversed the improvement effect of high-dose SGP on myocardial fibrosis in heart failure rats after myocardial infarction. CONCLUSIONS Shenge powder may inhibit myocardial fibrosis in heart failure rats after myocardial infarction by inhibiting the LOXL2/TGF-β1/IL-11 pathway.
Animals ; Male ; Rats, Sprague-Dawley ; Myocardial Infarction/complications* ; Transforming Growth Factor beta1/metabolism* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Heart Failure/pathology* ; Myocardium/metabolism* ; Fibrosis ; Amino Acid Oxidoreductases/metabolism* ; Interleukin-11/metabolism* ; Tissue Inhibitor of Metalloproteinase-1/metabolism* ; Matrix Metalloproteinase 9/metabolism*

OBJECTIVE: To investigate the safety and efficacy of avatrombopag（AVA） combined with rhIL-11 in treating thrombocytopenia induced by chemotherapy in acute myeloid leukemia. METHODS: The clinical information of 8 patients in the real world who received avatrombopag combined with rhIL-11 in cancer treatment-induced thrombocytopenia(CTIT) after AML chemotherapy were retrospectively analyzed, and at the same time, 8 patients who received rhIL-11 only in CTIT after AML chemotherapy served as the control group, A preliminary observation was to summarize and compare the therapeutic efficacy and adverse effects between the two groups. RESULTS: D3 and D7 platelet counts were not significantly different between the observation group and the control group after treatment. The platelet counts in the observation group was significantly higher than those of the control group on the 10th day after treatment (P < 0.01). The adverse reactions, such as weakness, abdominal pain, fatigue, nausea and edema after treatment were mild in the observation group and the control group. Except for one patient in the observation group who had a history of cerebral infarction before the onset of the disease and was routinely taking antiplatelet drugs, no thrombosis events occurred in the patients in the observation and control groups during the period of administration of the drug, and the total incidence rate of adverse reactions was not significantly different between the two groups. CONCLUSION The combination of AVA and rhIL-11 can enhance platelet recovery in CTIT of AML patients after chemotherapy. Compared with the rhIL-11 alone group, the platelet recovery time in AVA+rhIL-11 group was significantly shorter, the platelet count on the 10th day after drug administration was significantly higher. No statistically significant difference in the total incidence rate of adverse reactions was observed between rhIL-11 alone group and AVA+rhIL-11 group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Thrombocytopenia/chemically induced* ; Interleukin-11/therapeutic use* ; Retrospective Studies ; Adult ; Thiophenes/therapeutic use* ; Platelet Count ; Female ; Male ; Middle Aged ; Thiazoles

OBJECTIVE: To analyze and compare the efficacy of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of thrombocytopenia after chemotherapy in acute leukemia patients. METHODS: 180 patients with acute leukemia complicated with thrombocytopenia after chemotherapy in the First Affiliated Hospital of Anhui Medical University were analyzed retrospectively. Among them, 50 patients who treated with rhTPO and did not receive platelet transfusion were set as group A, 50 patients treated with rhTPO and receive platelet transfusion were set as group B, Forty patients treated with rhIL-11 without platelet transfusion were set as group C, Forty patients who treated with rhIL-11 and received platelet transfusion were set as group D. The duration of PLT below 20×10⁹/L, the days it takes for PLT to recover to more than 100×10⁹/L, and the incidence of different bleeding degrees were compared among several groups. RESULTS: The duration of PLT<20×10⁹/L in group A(3.72±1.14 d) was significantly shorter than that in group C(4.93±1.33 d) (P<0.001), and there was no significant difference from group B (P>0.05). The duration of PLT<20×10⁹/L in group B(3.06±0.91 d) was significantly shorter than that in group D(4.65±0.98 d) (P<0.001), while the difference in duration of days between group C and D was not statistically significant (P>0.05). The times for PLT to recover to 100×10⁹/L in group A(13.46±1.67 d) were significantly shorter than that in group C(16.85±2.13 d) (P<0.05), but there was no significant difference from group B (P>0.05). The time required for PLT to recover to 100×10⁹/L in group B(13.36±1.49 d) were significantly shorter than that in group D(16.18±1.78 d) (P<0.05), while the difference in the days required for group C and group D was not statistically significant (P>0.05). The incidence of high bleeding risk in group B was significantly lower than that in group A (22% vs 44%, P<0.05), the incidence of high bleeding risk in group D was significantly lower than that in group C (32% vs 65%, P<0.05), and the incidence of high bleeding risk in group A was significantly lower than that in group C (44% vs 65%, P<0.05). The incidence of high bleeding risk in group B(22%) was lower than that in group D(32.5%), and the difference was not statistically significant (P>0.05). CONCLUSION In the treatment of acute leukemia patients with thrombocytopenia after chemotherapy, compared with rhIL-11, rhTPO can significantly shorten the duration for patients in a status with extremely low levels of PLT and the recovery time of PLT to normal range. In addition, PLT transfusion cannot speed up the time for patients to raise platelets to a safe range, nor can it shorten the duration of low PLT levels, but it can reduce the incidence of high bleeding risk events.
Humans ; Interleukin-11 ; Leukemia, Myeloid, Acute/drug therapy* ; Platelet Count ; Recombinant Proteins/therapeutic use* ; Retrospective Studies ; Thrombocytopenia ; Thrombopoietin/therapeutic use*

OBJECTIVE: To analyze the relationship between serum miR-34a level and thrombocytopenia after chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 69 eligible DLBCL patients who received chemotherapy in our hospital from January 2018 to January 2020 were prospectively included as the research subjects, all patients received R-CHOP 21 regimen (rituximab + cyclophosphamide + adriamycin + vincristine + prednisone) for chemotherapy, 3 weeks was 1 cycle, and 2 cycles of chemotherapy were used. The patients were divided into a reduction group and a non reduction group according to whether there was thrombocytopenia after chemotherapy, the general data and laboratory indexes of the two groups were investigated and compared, the relationship between serum miR-34a before chemotherapy and thrombocytopenia after chemotherapy in patients was analyzed. RESULTS: Among the 69 DLBCL patients, 36 patients developed thrombocytopenia after 2 cycles of R-CHOP 21 regimen for chemotherapy, the incidence was 52.17%; the level of serum IL-11 and the relative expression of miR-34a mRNA in the reduction group were significantly lower than the non reduction group (P<0.05), compared other data between groups, there was no statistical significant difference (P>0.05); after Logistic regression analysis, the results showed that the level of serum IL-11 and the relative expression of miR-34a mRNA were related to thrombocytopenia after chemotherapy in DLBCL patients, low expression of each index may be a risk factor of thrombocytopenia after chemotherapy in DLBCL patients (OR>1, P<0.05); ROC curve was drawn, and the results showed that the AUC of serum IL-11 level and miR-34a mRNA relative expression before chemotherapy alone and in combination predicted the risk of thrombocytopenia after chemotherapy in DLBCL patients were all >0.80, and the predictive value was ideal, when the cut-off value of serum IL-11 level before chemotherapy was 42.094 pg/ml, and the cut-off value of miR-34a mRNA relative expression was 3.894, the combined prediction value was the best. CONCLUSION The relative expression of miR-34a mRNA is associated with thrombocytopenia after chemotherapy in DLBCL patients, which may be a risk factor for thrombocytopenia in patients after chemotherapy, has certain value in predicting the risk of thrombocytopenia of patients after chemotherapy.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cyclophosphamide ; Doxorubicin ; Humans ; Interleukin-11/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/genetics* ; MicroRNAs/genetics* ; Prednisone/therapeutic use* ; Prognosis ; RNA, Messenger ; Rituximab/therapeutic use* ; Thrombocytopenia ; Vincristine

OBJECTIVE: To explore the intervention effect of recombinant human interleukin-11 (rhIL-11) and recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the duration and severity of agranulocytosis in patients with hematological malignancies after chemotherapy, and to analyze the influencing factors. METHODS: The data of hematological malignancy patients treated with rhIL-11 and rhG-CSF after chemotherapy in the hematology department of The First Hospital of Lanzhou University from July 2017 to July 2020 were collected retrospectively. The duration and differences of agranulocytosis in differeent groups were compared by univariate analysis, and the influencing factors of agranulocytosis duration were further analyzed by multiple regression analysis. RESULTS: The duration of agranulocytosis in 97 patients was 6.47±2.93 days. The results of univariate analysis showed that there were no statistical differences in the duration of agranulocytosis among patients with different sex, age, height, weight, body surface area, body mass index (BMI), dose of rhG-CSF, dose of rhIL-11, spontaneous bleeding after administration of rhG-CSF and rhIL-11, and the duration of agranulocytosis in patients with different red blood cell count (RBC), hemoglobin(HGB) level, platelet count (PLT) and absolute neutrophil count (ANC), before administration of rhG-CSF and rhIL-11. There were significant differences in agranulocytosis time among patients with different disease types, chemotherapy cycle, fever after rhG-CSF and rhIL-11 administration, and different white blood cell count (WBC) baseline level before rhG-CSF and rhIL-11 administration (P＜0.05). Compared with patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), patients with acute myeloid leukemia (AML) had the longest duration of agranulocytosis, which was 7.07±3.05 d. Compared with patients with chemotherapy cycles of 4－6 and ≥7, patients with total chemotherapy cycle of 1－3 had the shortest duration of agranulocytosis, which was 5.25±2.48 d. Compared with patients without fever, patients with fever within 1 day after administration of cytokines and patients with fever within 2-5 days after administration of cytokines, the duration of agranulocytosis was the longest in patients with fever 6 days after administration of cytokines, which was 8.85±2.85 d. Compared with patients with WBC baseline <1.0×10⁹/L, (1.0－1.9)×10⁹/L and (2.0－3.9)×10⁹/L, patients with WBC baseline ≥4.0×10⁹/L had the shortest duration of agranulocytosis, which was 4.50±2.56 d. Multiple linear regression analysis showed that chemotherapy cycle, different fever after administration of rhG-CSF and rhIL-11, diagnosis of ALL and NHL, and WBC baseline level before administration of rhG-CSF and rhIL-11 were the influencing factors of the duration of agranulocytosis (P＜0.001). CONCLUSION The risk of prolonged agranulocytosis is higher in patients diagnosed with AML, with more chemotherapy cycles, lower WBC baseline before cytokines administration and fever later after cytokines administration, which should be paid more attention to.
Agranulocytosis ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Hematologic Neoplasms/drug therapy* ; Humans ; Interleukin-11 ; Lymphoma, Non-Hodgkin/drug therapy* ; Recombinant Proteins/therapeutic use* ; Retrospective Studies

OBJECTIVETo study the therapeutic efficacy of multigly-cosidorum Tripterygium combined with rhIL-11 for treating patients with immune thrombocytopenia (ITP).

METHODSA total of 75 patients with ITP were divided into 2 group: experimental group and control group. The experimental group included 40 patients who had been treated with multigly-cosidorum Tripterygium combined with rhIL-11. Multigly-cosidorum Tripterygium was given at a dose of 1mg/kg·d for 2 months and rhIL-11 was injected at a dose of 16,000,000 units per day. Control group included 35 patients who had been treated with prednisone at a dose of 1 mg/kg·d. Platelet counts were performed every day before platelet counts >30 × 10⁹/L. Peripheral blood T cells were collected before and after treated for 2 months. The ratios of CD4⁺, CD8⁺ T cells in peripheral blood T cells were analyzed by flow cytometry.

RESULTSTotally effective rate in experimental group was 77.5%. Totally effective rate in control group was 82.9%. Totally effective rate showed no statistical difference between these two groups (P > 0.05). The average time of platelet count 30 × 10⁹/L in experimental and control groups were 13.06 ± 6.10 days and 9.76 ± 5.71 days respectively; in experimental group, the ratio of CD4⁺ T cells in peripheral blood was 21.03% before treatment, then rised to 34.49% after treatment for 2 months (P < 0.01); The ratio of CD8⁺ T cells in peripheral blood was 26.35% before treatment, then decreased to 20.18% (P < 0.01). In control group, the ratio of CD4⁺ T cells was 22.30% before treatment, then rised to 25.11% after treatment for 2 months (P < 0.05); The ratio of CD8⁺ T cells in peripheral blood was 27.24% before treatment, then decreased to 21.35% (P < 0.01).

CONCLUSIONMultigly-cosidorum tripterygium can correct disorder of T lymphocytes, the combination of multigly-cosidorum triptergium and rhIL-11 can accelerate therapeutic efficacy for treating ITP and with less adverse reaction, so this combination may be effective and safe for treating patients with ITP.

Antineoplastic Agents ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Interleukin-11 ; therapeutic use ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Recombinant Proteins ; therapeutic use ; T-Lymphocytes ; Tripterygium ; chemistry

OBJECTIVETo investigate and evaluate the clinical therapeutic effect of low-dose interleukin-11 treatment of thrombocytopenia in patients with malignant hematologic diseases after chemotherapy.

METHODS70 patients with hematologic malignancies including acute leukemia, lymphoma and multiple myeloma were randomly divided into treatment group (35 cases) and control group (35 cases) and were treated with chemotherapy. Cases in the treatment group received subcutaneous injection of interleukin-11 (50 µg × kg(-1) × d(-1)) until platelet counting recovered ≥ 50 × 10(9)/L, while cases in the control group were not administrated with interleukin-11.

RESULTSThe mean time of platelet recovery in the treatment group was 9.6 days, significantly shorter than that (14.0 days) in the control group (P < 0.05). The minimum platelet counting in the treatment group was significantly higher than that in the control group (16.2 × 10(9)/L vs. 11.6 × 10(9)/L, P < 0.05). The mean times of platelet infusion after chemotherapy in the treatment group and control group were 2.88 and 2.98, respectively (P > 0.05).

CONCLUSIONAdministration of interleukin-11 in thrombocytopenic patients with hematologic malignancies after chemotherapy may not only remarkably enhance platelet counts and shorten the recovery time of thrombocytopenia, but also has only mild side effects.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Female ; Humans ; Interleukin-11 ; administration & dosage ; therapeutic use ; Leukemia ; drug therapy ; Lymphoma ; drug therapy ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Platelet Count ; Thrombocytopenia ; chemically induced ; therapy ; Young Adult

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

Traditional treatment of chronic idiopathic thrombocytopenic purpura (CITP) is usually adopted as hormonal therapy. If necessary, it also can be given immunosuppressive therapy. In order to investigate the curative effect of rhIL-11 on patients with ITP, 26 patients were divided into control group and rhIL-11 group, each group with 13 patients. Control group was given traditional hormonal therapy and immunosuppressive therapy, while rhIL-11 group was given rhIL-11 on base of traditional therapy. rhIL-11 25 microg/(kg.d) was injected s.c. for 28 days. The results showed that 23 out of 26 patients obtained obviously curative effect in platelet count, especially in rhIL-11 group, but another 3 patients had no response on therapy. The platelet counts of control and rhIL-11 groups increased from 26.15 x 10(9)/L and 27.84 x 10(9)/L before treatment to 66.62 x 10(9)/L and 105.62 x 10(9)/L after treatment. The platelet count of rhIL-11 group after treatment was remarkably higher than that of the control group (p < 0.05). Platelet count of 8 patients in rhIL-11 group recovered to normal. It is concluded that rhIL-11 combined with traditional hormone-immuno-suppressive therapy is effective to CITP.
Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Interleukin-11 ; therapeutic use ; Male ; Middle Aged ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; therapy ; Recombinant Proteins ; therapeutic use ; Treatment Outcome

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