Evaluation of Clinical Efficacy of Shengmaisan Granules in Inhibiting Myocardial Fibrosis in Patients with Chronic Heart Failure with Qi-Yin Deficiency Syndrome Based on CMR / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Shengmaisan granules on myocardial fibrosis in chronic heart failure patients with Qi-Yin deficiency syndrome by cardiac magnetic resonance （CMR） imaging and serological indicators. MethodSixty-six chronic heart failure patients with Qi-Yin deficiency syndrome who visited the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine， Nanjing University of Chinese Medicine from October 2021 to January 2023 were selected. The patients were assigned into a control group （33 cases） and an observation group （33 cases） by the minimization random method. Both groups received standardized Western medicine treatment for heart failure. In addition， the control group was treated with placebo granules， and the observation group with Shengmaisan granules for a course of 6 months. The baseline data， clinical efficacy， TCM symptom scores， serological indicators ［high-sensitivity C-reactive protein （hs-CRP）， soluble growth stimulation expressed gene 2 protein （sST2）， pro-collagen Ⅲ N-terminal peptide （PⅢNP）， interleukin （IL）-6， IL-11， transforming growth factor-β1 （TGF-β1）］， echocardiography ［Left atrial diameter （LAD）， left ventricular end systolic diameter （LVEDs）， left ventricular end diastolic diameter （LVEDd）］ and CMR indicators ［left ventricular ejection fraction （LVEF）， myocardial extracellular volume fraction （ECV）， and longitudinal relaxation time （T1）］ were compared between the two groups. ResultFinally， 31 patients in the control group and 30 patients in the observation group were included. There was no significant difference in baseline data or indicators between the two groups before treatment. Compared with those before treatment， the scores of TCM symptoms （shortness of breath， fatigue， palpitations， spontaneous or night sweats， thirst/dry throat， feverish feeling in palms and soles， and edema in lower limbs）， total score of TCM symptoms， ECV， T1， inflammation/fibrosis indicators （hs-CRP， sST2， PⅢNP， IL-6， IL-11， and TGF-β1） in observation group decreased （P<0.05， P<0.01）， and the scores of TCM symptoms （except feverish feeling in palms and soles）， T1， and inflammation/fibrosis indicators in the control group decreased （P<0.05， P<0.01）. After treatment， the observation group had lower scores of TCM symptoms （except feverish feeling in palms and soles and edema in lower limbs）， ECV， T1， and inflammation/fibrosis indicators than the control group （P<0.05， P<0.01）. After treatment， the total response rate in the observation group was 93.33% （28/30）， which was higher than that （80.65%， 25/31） in the control group （Z=2.976， P<0.01）. There was no significant difference in adverse reactions between the two groups during treatment. ConclusionFor patients with chronic heart failure with Qi-Yin deficiency syndrome， Shengmaisan Granules can alleviate the TCM symptoms， reduce inflammation， and inhibit myocardial fibrosis by regulating the TGF-β1/IL-11 signaling axis.

Analysis of Agranulocytosis Time and Its Influencing Factors in Patients with Hematological Malignancies Treated with rhIL-11 combined rhG-CSF / 中国实验血液学杂志

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.

Effect of rhTPO and rhIL-11 on Thrombocytopenia after Chemotherapy in Leukemia / 中国实验血液学杂志

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.

Research progress on the promoting effect of interleukin-11 on tumors / 上海交通大学学报（医学版）

According to the lastest statistics, the overall morbidity and mortality of cancer in China still show an upward trend compared with historical data. An in-depth understanding of the molecular mechanisms of tumorigenesis and development is important to formulate future treatment strategies. Interleukin 11 (IL-11) is a member of cytokines that traditionally promote megakaryocyte maturation and regulate immune activity. In recent years, the promoting effect of IL-11 on tumor has been gradually discovered. This review mainly expounds that IL-11 is regu-lated by transforming growth factor-β/drosophila mothers against decapentaplegic protein (TGF-β/Smad) pathway, and may play a role in tumor-igenesis, drug resistance, metastasis and tumor microenvironment through signal transduction pathways such as Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway, and explores the application prospect of interfering IL-11 signal transduction in tumor therapy.

Cancer-Associated Fibroblasts Promote the Chemo-resistance in Gastric Cancer through Secreting IL-11 Targeting JAK/STAT3/Bcl2 Pathway / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Our aim was to detect the potential role of interleukin 11 (IL-11) in the development of chemo-resistance in gastric cancer and to reveal the mechanism involved in the process. MATERIALS AND METHODS: Here, we used flow cytometry to examine the percentage of cancer-associated-fibroblasts in tumor samples from chemo-resistant and -sensitive gastric cancer patients. Using MTT assay, we detected the cell viability under different conditions. Using quantitative real-time polymerase chain reaction and Western blotting, we determined the target expressions in mRNA and protein levels. We also performed immunohistochemistry and immunofluorescence to detect the target proteins under different conditions. Animal models were constructed to verify the potential role of IL-11 in chemo-resistant develop in vivo. RESULTS: Herein, we observed enriched cancer associated fibroblasts in drug resistant tumor tissues from gastric patients. Those fibroblasts facilitate the chemotherapeutic drugs resistance development through the secretion of IL-11, which activates the IL-11/IL-11R/gp130/JAK/STAT3 anti-apoptosis signaling pathway in gastric cancer cells. We found that the combination of chemotherapeutic drugs and JAK inhibitor overcomes the resistance and increases the survival of mice with gastric cancer xenografts. CONCLUSION: Ourresults demonstrated that IL-11 contributed to the obtain ofresistance to chemotherapy drugs through gp130/JAK/STAT3/Bcl2 pathway, and targeting the IL-11 signaling pathway induced by fibroblasts might be a promising strategy to overcome the multi-drugs resistant cancer in clinic.

Consensus on clinical diagnosis, treatment and prevention management of chemotherapy induced thrombocytopenia in China(2018) / 中华肿瘤杂志

Chemotherapy induced thrombocytopenia (CIT) is a common side-effect of chemotherapy in cancer patients, which lead to dose and cycle reduction or chemotherapy delay, or even the need of platelet transfusion. Therefore, CIT significantly increases the cost of treatment, reduces the efficacy of chemotherapy and the quality of life, and shortens the survival time of patients. The main treatments of CIT include transfusion of platelets, recombinant human thrombopoietin (rhTPO), and recombinant human interleukin-11 (rhIL-11). RhIL-11 is the first approved thrombocytopoietic cytokine. Interleukin-11 has been shown to be effective in the treatment of thrombocytopenia. RhTPO is a recombinant full-length glycosylated thrombopoietin, which is a ligand for c-Mpl protein. Several observations indicated that administration of rhTPO before and after chemotherapy might be beneficial to patients, which enhances platelet recovery and reduces thrombocytopenia after moderately myelosuppressive regimens. In recent years, the application of rhTPO in CIT treatment has dramatically changed the management and treatment plan of CIT. The China Society of Clinical Oncology (CSCO) published a consensus on CIT in 2014. Based on this, the expert committee updated "Consensus on clinical diagnosis, treatment and prevention management of chemotherapy induced thrombocytopenia in China (2018)" according to the recent literature and clinical research. The new evidence-based practice consensus for CIT aims to provide more reasonable diagnosis, treatment of prevention regimens for CIT patients to maintain the normal platelet counts.

Lysophosphatidic acid enhances breast cancer cells-mediated osteoclastogenesis

Lysophosphatidic acid (LPA) is known to play a critical role in breast cancer metastasis to bone. In this study, we tried to investigate any role of LPA in the regulation of osteoclastogenic cytokines from breast cancer cells and the possibility of these secretory factors in affecting osteoclastogenesis. Effect of secreted cytokines on osteoclastogenesis was analyzed by treating conditioned media from LPA-stimulated breast cancer cells to differentiating osteoclasts. Result demonstrated that IL-8 and IL-11 expression were upregulated in LPA-treated MDA-MB-231 cells. IL-8 was induced in both MDA-MB-231 and MDA-MB-468, however, IL-11 was induced only in MDA-MB-231, suggesting differential LPARs participation in the expression of these cytokines. Expression of IL-8 but not IL-11 was suppressed by inhibitors of PI3K, NFkB, ROCK and PKC pathways. In the case of PKC activation, it was observed that PKCδ and PKCμ might regulate LPA-induced expression of IL-11 and IL-8, respectively, by using specific PKC subtype inhibitors. Finally, conditioned Medium from LPA-stimulated breast cancer cells induced osteoclastogenesis. In conclusion, LPA induced the expression of osteolytic cytokines (IL-8 and IL-11) in breast cancer cells by involving different LPA receptors. Enhanced expression of IL-8 by LPA may be via ROCK, PKCu, PI3K, and NFkB signaling pathways, while enhanced expression of IL-11 might involve PKCδ signaling pathway. LPA has the ability to enhance breast cancer cells-mediated osteoclastogenesis by inducing the secretion of cytokines such as IL-8 and IL-11.

Clinical research of thrombocytopenia induced by craniospinal irradiation / 中华放射肿瘤学杂志

Objective@#To evaluate the clinical efficacy and adverse events of recombinant human interleukin-11(rhIL-11) in the prevention of thrombocytopenia induced by craniospinal irradiation.@*Methods@#In this randomized control study, 100 patients were randomly divided into A (rhIL-11 group, n=50) and B groups (control group, n=50). In the A group, subcutaneous injection of rhIL-11 was delivered at a dose of 50 μg/kg/d, once daily when the platelet count was< 100×109/L during radiotherapy or decreased by> 50% compared with the baseline level. The administration of rhIL-11 was terminated when the platelet count was ≥ 200×109/L. In the B group, the same protocol was conducted when the platelet count was< 50×109/L and terminated until the platelet count was ≥ 100×109/L. The clinical efficacy was assessed in 92 patients. Subcutaneous injection of rhIL-11 could significantly elevate the minimal platelet count during craniospinal irradiation (P<0.01), considerably shorten the duration of thrombocytopenia (P<0.01) and effectively shorten the duration of radiotherapy (P<0.01). Main adverse events included mild pain at the injection site, sclerosis, redness and fatigue, etc.@*Conclusions@#Injection of rhIL-11 can significantly enhance the platelet count, effectively reduce the incidence of thrombocytopenia throughout craniospinal irradiation, guarantee the success of radiotherapy and yield mild adverse events.

Recombinant human interleukin-11 for chemotherapy-induced thrombocytopenia of acute leukemia: a multi-center study / 白血病·淋巴瘤

Objective@#To explore the efficacy and safety of recombinant human interleukin-11 (rhIL-11) in treatment of chemotherapy-induced thrombocytopenia of acute leukemia.@*Methods@#Acute leukemia patients with chemotherapy-induced thrombocytopenia [Platelets (Plt) < 50×109/L] in 6 centers nationwide from February 2016 to July 2016 were treated with rhIL-11 (2 mg/time, twice per day) by subcutaneous injection. Treatment lasted 7 days or at least until Plt≥ 50×109/L. The Plt recovery was observed during treatment.@*Results@#A total of 112 patients were enrolled, and 2 patients decided to drop out of study. The efficacy population consisted of 110 patients, and the total response rate reached 74.5% (82/110). The average variation of Plt during treatment was (70±54)×109/L, and recovery average time of Plt for the patients with favorable efficacy was (8.7±3.0) days. In treatment with severe thrombocytopenia, rhIL-11 alone could shorten the recovery time compared with rhIL-11 combined with Plt transfusion [(8.0±2.6) d vs. (9.6±3.5) d, t=2.17, P=0.03].@*Conclusion@#rhIL-11 twice a day of subcutaneous injection can effectively promote Plt recovery and reduce Plt transfusion with less adverse reactions, which is worthy of further application.

Effect of IL-11 on the invasive and metastatic abilities of anaplastic thyroid carcinoma cells / 中华耳鼻咽喉头颈外科杂志

Objective@#To explore the effect of hematopoietic cytokines IL-11 on invasion and metastasis abilities of anaplastic thyroid cacinoma(ATC) cells.@*Methods@#Real-time PCR was performed for examining the IL-11 mRNA expression in thyroid carcinoma cell lines, and IL-11 protein expression in the supernament of thyroid carcinoma cell lines was detected by ELISA. Molecular cloning was employed to construct IL-11 stable knockdown cell line; MTT assay was used to analyze the effect of IL-11 on the proliferation of ATC cells; Transwell and wound healing assays were employed to analyze the abilities of migration and invasion in ATC cells. Western blotting was used to detect the relative pathway proteins. SPSS statistical package 19.0 was used to analyze the date, and Student′s t test was used for multiple comparisons.@*Results@#The protein level of IL-11 were significantly lower in knock-down cell lines than that in negative control cell lines(21.55±1.69, 16.18±0.85, 26.37±2.00 vs 54.54±3.99, all P<0.05). Colony formation assays reveal that colony number between knock-down cells and negative control cells has no significance(P>0.05). Meanwhile, MTT assays show that there is no significance between knock-down cell lines and negative control cell line(P>0.05). However, Transwell invasion and migration assays show that number of migrated cells is increased when ATC cells were treated with rhIL-11(0-100 ng/ml)at increasing concentrations.@*Conclusion@#IL-11 improves the migratory and invasive abilities of ATC cells via inducing EMT of ATC cells, and it can be used as a potential target for ATC molecular targeted therapy.

Synthesis and biological evaluation of 18F-AlF-NOTA-c (CGRRAGGSC) / 中华核医学与分子影像杂志

Objective To synthesize 18F-AlF-1,4,7-triazacyclononane-l,4,7-triacetic acid (NOTA)-c (CGRRAGGSC),which could specifically bind to the α chain of interleukin (IL)-11 receptor (IL-11 R),and evaluate its targeting potential to IL-11 R-positive tumors.Methods Polypeptide c (CGRRAGGSC) was first coupled with NOTA and then labeled with 18F by AlF labeling method.The radiochemical purity and radiochemical yield of 18F-AlF-NOTA-c(CGRRAGGSC) were analyzed by high performance liquid chromatography,and the stability in vitro was evaluated.The tracer biodistribution in tumor-bearing mice (cell line SKOV3) was evaluated by the dynamic imaging with microPET 30 min,1 h,2 h after injection of 18F-AlF-NOTA-c (CGRRAGGSC).The tracer kinetics was performed in normal mice.Pharmacokinetics parameters were calculated using DAS2.0 software.Results The radiochemical purity of 18F-AlF-NOTA-c(CGRRAGGSC) was higher than 95％ and the radiochemical yield was (30.0±7.4)％.It could be stably maintained in phosphatebuffered solution and plasma for at least 2 h.MicroPET imaging showed that 18F-AlF-NOTA-c(CGRRAGGSC)had a good affinity to SKOV3 tumor.The tumor/muscle ratios at 30 min,1 h,2 h after the injection of 18F-AlF-NOTA-c(CGRRAGGSC) were 6.26±2.98,7.19±3.63 and 9.05±4.30,respectively.The tracer was cleared rapidly in blood and mainly excreted by the liver and kidneys.The T1/2α and T1/2β were (0.38±0.14) h and (2.64±0.28) h,respectively.Conclusions 18F-AlF-NOTA-c(CGRRAGGSC) is easy to be synthesized and has a good affinity to IL-11R-positive tumors.It will be a potential IL-11R-targeting imaging agent.

Consensus on clinical diagnosis, treatment and prevention management of chemotherapy induced thrombocytopenia in China(2018) / 中华肿瘤杂志

Chemotherapy induced thrombocytopenia (CIT) is a common side-effect of chemotherapy in cancer patients, which lead to dose and cycle reduction or chemotherapy delay, or even the need of platelet transfusion. Therefore, CIT significantly increases the cost of treatment, reduces the efficacy of chemotherapy and the quality of life, and shortens the survival time of patients. The main treatments of CIT include transfusion of platelets, recombinant human thrombopoietin (rhTPO), and recombinant human interleukin-11 (rhIL-11). RhIL-11 is the first approved thrombocytopoietic cytokine. Interleukin-11 has been shown to be effective in the treatment of thrombocytopenia. RhTPO is a recombinant full-length glycosylated thrombopoietin, which is a ligand for c-Mpl protein. Several observations indicated that administration of rhTPO before and after chemotherapy might be beneficial to patients, which enhances platelet recovery and reduces thrombocytopenia after moderately myelosuppressive regimens. In recent years, the application of rhTPO in CIT treatment has dramatically changed the management and treatment plan of CIT. The China Society of Clinical Oncology (CSCO) published a consensus on CIT in 2014. Based on this, the expert committee updated "Consensus on clinical diagnosis, treatment and prevention management of chemotherapy induced thrombocytopenia in China (2018)" according to the recent literature and clinical research. The new evidence-based practice consensus for CIT aims to provide more reasonable diagnosis, treatment of prevention regimens for CIT patients to maintain the normal platelet counts.

Inhibitors of DNA methylation support TGF-β1-induced IL11 expression in gingival fibroblasts

PURPOSE: Oral wound healing requires gingival fibroblasts to respond to local growth factors. Epigenetic silencing through DNA methylation can potentially decrease the responsiveness of gingival fibroblasts to local growth factors. In this study, our aim was to determine whether the inhibition of DNA methylation sensitized gingival fibroblasts to transforming growth factor-β1 (TGF-β1). METHODS: Gingival fibroblasts were exposed to 5-aza-2'-deoxycytidine (5-aza), a clinically approved demethylating agent, before stimulation with TGF-β1. Gene expression changes were evaluated using quantitative polymerase chain reaction (PCR) analysis. DNA methylation was detected by methylation-sensitive restriction enzymes and PCR amplification. RESULTS: We found that 5-aza enhanced TGF-β1-induced interleukin-11 (IL11) expression in gingival fibroblasts 2.37-fold (P=0.008). 5-aza had no significant effects on the expression of proteoglycan 4 (PRG4) and NADPH oxidase 4 (NOX4). Consistent with this, 5-aza caused demethylation of the IL11 gene commonly next to a guanosine (CpG) island in gingival fibroblasts. The TGF-β type I receptor kinase inhibitor SB431542 impeded the changes in IL11 expression, indicating that the effects of 5-aza require TGF-β signaling. 5-aza moderately increased the expression of TGF-β type II receptor (1.40-fold; P=0.009), possibly enhancing the responsiveness of fibroblasts to TGF-β1. As part of the feedback response, 5-aza increased the expression of the DNA methyltransferases 1 (DNMT1) (P=0.005) and DNMT3B (P=0.002), which are enzymes responsible for gene methylation. CONCLUSIONS: These in vitro data suggest that the inhibition of DNA methylation by 5-aza supports TGF-β-induced IL11 expression in gingival fibroblasts.

Expressions of interleukin-11 and interleukin-11 receptorαin non-small cell lung cancer cell lines and their clinical significances / 肿瘤研究与临床

Objective To detect the expressions of interleukin-11 (IL-11) and interleukin-11 receptorα(IL-11Rα) in non-small cell lung cancer (NSCLC) cell lines, and explore their clinical significances. Methods The expressions of IL-11 and IL-11Rαin NSCLC cell lines A549, H2228, healthy lung small airway epithelial cell (SAEC) line cytoplasm, cell membrane and nucleus were detected by Western blot. Results The expressions of IL-11 and IL-11Rα were low in the cell membrance and nucleus (cell membrane: IL-110.04± 0.03, IL-11Rα0.05±0.03; nuclear: IL-110.45±0.19, IL-11Rα0.07±0.02;P<0.01); The expressions of IL-11 and IL-11Rα in A549 and H2228 cell lines were significantly increased compared with those of SAEC cell lines in the cell membrance and cytoplasm (P< 0.01); Among the A549 cell lines, the expressions of IL-11 and IL-11Rα in cell nucleus were much higher than those of the cell membrance and cytoplasm (P< 0.01). Among the H2228 cell lines, the expression of IL-11 in cytoplasm was the highest and the expression of IL-11Rα was the highest in the cell nucleus (P< 0.01). Conclusion The expressions of IL-11 and IL-11Rαare high in NSCLC cell lines, and it is good for the screening and early diagnosis of lung cancer by detecting the expressions of IL-11 and IL-11Rα.

Clinical observation of arrhythmia after treatment with recombinant human interleukin 11 in elderly patients with myelodysplastic syndromes / 白血病·淋巴瘤

Objective To analyze the arrhythmia after treatment with recombinant human interleukin 11 (rhIL-11) because of down-regulating platelet in elderly patients with myelodysplastic syndromes (MDS), and to investigate the possible mechanism of arrhythmia induced by in MDS patients. Methods The data of 2 MDS patients with arrhythmia after rhIL-11 therapy were analyzed retrospectively. The patients'hemoglobin, electrocardiogram (ECG), myocardial enzymes, cardiac troponin Ⅰ (cTnⅠ), N-terminal pro brain natriuretic peptide (NT-proBNP) changes, as well as cardiac ultrasonography and Holter monitoring during arrhythmia were dynamically observed before and after use of rhIL-11, at the time of arrhythmia and restoring sinus rhythm after the withdrawal of rhIL-11. Results Before the use of rhIL-11, blood platelet count of patient 1 and patient 2 was 2×109/L and 3×109/L respectively. Arrhythmias occurred in the two patients at 11st and 14th days respectively. ECG showed atrial fibrillation with rapid ventricular rate, and dynamic ECG monitoring showed that syncope was caused by sinus arrest due to cardiac cardiogenic syncope. Heart ultrasound prompted ejection fraction (EF) values in the normal range. Creatine kinase, creatine kinase isoenzymes, aspartate transaminase, lactate dehydrogenase, and cTnⅠ had no obvious increase or decrease after rhIL-11 treatment, but NT-proBNP was increased significantly. After discontinuation of rhIL-11 and diuretic treatment, no syncope occurred. ECG restored sinus rhythm, and NT-proBNP was decreased significantly. Conclusion rhIL-11 in elderly MDS patients may induce arrhythmia, which can be restored after drug withdrawal, limited sodium diet and diuretic treatment, but much attention should be paid to the heart-related symptoms and signs, dynamic monitoring of NT-proBNP and timely treatment.

Establishment of a pharmacokinetic detection method for PEGylated recombinant human interleukin-11 mutein in cynomolgus monkeys / 国际药学研究杂志

Objective To evaluate the pharmacokinetics, drug concentration and effect relationship of PEGylated IL-11 mutein (PEG-mIL11) in cynomolgus monkeys through the validated anti-PEG-ELISA method. Methods PEG-mIL11 at 350 μg/kg was subcutaneously injected in cynomolgus monkeys, and the blood samples were collected at various time points. An anti-PEG-ELISA method was validated and used to investigate the concentration of PEG-mIL11, and platelet counts were measured to explore the relationship of drug concentration and effect. Results Results of the validation test demonstrated that PEG-mIL11 in monkey blood could be quantitated by anti-PEG-ELISA. Its linear range was (26.34-200) ng/ml. The specificity, accuracy and precision of the method met the present criteria. The terminal elimination half-life (T1/2) of PEG-mIL11 was (13.4 ± 2.4) h, the peak time (Tmax) was (6.7 ± 2.3) h, the peak concentration (Cmax) was (2.4 ± 0.5) μg/ml, the area under curve (AUC)(0-t) was (77.7 ± 15.6) μg∙h/ml, and the clearance (CL) was (4.6 ± 0.8) ml/ (h·kg). The thrombopoietic effect did not relate directly with the concentration of PEG-mIL11 in serum. Conclusion Anti-PEG-ELISA, used in this study to measure the concentration of PEG-mIL11, is a steady, reliable and specific method for PEGmIL11 pharmacokinetic study, and its chemical modification by PEG possesses long circulating half-lives, thereby suggesting less frequency of administration.

Clinical Observation of Recombinant Human Interleukin-11 in the Treatment of Chemotherapy-induced Thrombocytopenia / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of recombinant human interleukin-11 (rhIL-11) in the treat-ment of chemotherapy-induced thrombocytopenia. METHODS:86 patients with thrombocytopenia induced by chemotherapy were selected and divided into control group and observation group according to random number table,with 43 cases in each group. Con-trol group was given platelet transfusion 10 IU,once every 2-3 d;observation group was given Recombinant human IL-11 for injec-tion 25-50 μg/kg,qd. Both groups received treatment for 14 d. Clinical efficacies of 2 groups were observed as well as platelet count before and after treatment. The duration of platelet decrease and recovery,the occurrence of ADR were compared between 2 groups. RESULTS:The total effective rate of observation group was 81.40%,which was significantly higher than 62.79% of con-trol group,with statistical significance (P0.05);after treatment,platelet count of 2 groups increased significantly,and the observation group was significant-ly higher than the control group,with statistical significance(P0.05). CON-CLUSIONS:rhIL-11 shows good therapeutic efficacy in the treatment of chemotherapy-induced thrombocytopenia,and can signifi-cantly improve platelet count,shorten the duratione of platelet decrease and recovery with good safety.

Clinical observation of recombinant human interleukin-11 combined with prednisone in the treatment of adult recurrent primary immune thrombocytopenia / 中国基层医药

Objective To investigate the effect and adverse reaction of recombinant human interleukin-11 ( rhIL-11) combined with prednisone in the treatment of adults with recurrent primary immune thrombocytopenia ( ITP) .Methods The clinical and laboratory data of 34 patients of adult recurrent ITP were retrospectively analyzed.16 cases in A group were treated with prednisone,18 cases in B group were treated with rhIL-11 combined with prednisone.Results The effective rate of B group was 44.5%,which of A group was 50.0%,there was no sig-nificant difference between the two groups(P>0.05).After 7d,10d,14d treatment,platelet count in B group were (39.7 ±16.3) ×109/L,(55.3 ±27.6) ×109/L,(71.8 ±30.9) ×109/L respectively,which in A group were (24.3 ±6.7) ×109/L,(35.6 ±28.6) ×109/L,(47.3 ±29.2) ×109/L respectively,the differences between the two groups were statistically significant(t=2.008,2.090,2.431,all P0.05%),but there were 2 cases of capillary leak syndrome(CLS) in B group.Conclusion rhIL-11 combined with prednisone can promote significant rebound of platelet in the adult patients with recurrent IPT in a short term,effectively control bleeding,and the side effect is controllable.

Effects of recombinant human interleukin-11 on the vaginal epithelium mitosis of estrone periodical mice and the expression of PCNA / 中国生化药物杂志

Objective To investigate the therapeutic effects of recombinant human interleukin-11 (rhIL-11) on the vaginal epithelium mitosis of estrone periodical mice and the exprssion of PCNA.Methods The vaginal epithelium mitosis of estrone periodical mice was used as the epidermis hyperplasia model, rhIL-11 action in regulating the epidermis hyperplasia was observed and the expression of PCNA was detected by immunohistochemistry.Results The rhIL-11 significantly inhibited the mitosis of mouse vaginal epithelium, decreased the expression of PCNA ( P <0.01).Conclusion The rhIL-11 has good efficacy in treating the epidermis hyperplasia of psoriasis by inhibiting the mitosis of epithelium and decreasing the expression of PCNA.

Effects of recombinant human interleukin 11(rhIL-11) on proliferation, migration and invasion of pulmonary adenocarcinoma A549 cells / 天津医药

Objective To observe the effects of recombinant human interleukin 11(rhIL-11) on proliferation, migration and invasion of A549 cells, and the mechanism thereof. Methods Final concentrations of 0, 10, 20, 50 and 100μg/L rhIL-11 were added into pulmonary adenocarcinoma A549 cells. The cell proliferation was detected by MTT. The wound-healing, transwell migration assay were used to validate the capability of the migration and invasion of A549 cells. Matrix metallopro-teinases (MMP)-2 and MMP-9 protein expressions were revealed by Western blot assay. Results The proliferation of A549 cells was not significantly changed by rhIL-11. The cell capability to migrate and invade was significantly increased 24 h af-ter treatment with rhIL-11 (P<0.05). The expression levels of MMP-2 and MMP-9 were significantly un-regulated, and which were increased with the increased concentrations of rhIL-11 (P<0.05). Conclusion rhIL-11 can promote the migra-tion and invasion of A549 cells, and the up-regulation of MMP-2 and MMP-9 expression might be one of the mechanisms.