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Interleukin 11: similar or opposite roles in female reproduction and reproductive cancer?

During placental development and carcinogenesis, cell invasion and migration are critical events in establishing a self-supporting vascular supply. Interleukin (IL)-11 is a pleiotropic cytokine that affects the invasive and migratory capabilities of trophoblast cells that form the placenta during pregnancy, as well as various malignant cell types. The endometrium is the site of embryo implantation during pregnancy; conversely, endometrial carcinoma is the most common gynaecological malignancy. Here, we review what is known about the role of IL-11 in trophoblast function and in gynaecological m

Соотношение уровней тромбопоэтина и интерлейкина-11 и тромбоцитопенсии, связанной с болезнью денге.

Одной из главных клинических исследований денге является тромбоцитопенсия. В ходе этой работы мы изучили уровни тромбопоэтина (TPO) и интерлейкина-11 (IL-11), двух наиболее мощных регуляторов производства тромбоцитов, в сыворотке 28 пациентов с лихорадкой денге (DF). Пациенты, имеющие DF, имели более высокий уровень TPO по сравнению со здоровыми людьми (p<0,005). Пациенты с геморрагической лихорадкой денге (DHF, n=7) - более тяжелая форма денге - имели более высокие уровни ТПО, чем пациенты с дифтерией (p<0,001). Уровни сериала TPO и количества тромбоцитов обратно коррелировали как у пациентов

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Thrombocytopenia is one of the main clinical findings of dengue. In this work we examined the levels of thrombopoietin (TPO) and interleukin-11 (IL-11), two of the most potent regulators of platelet production, in serum from 28 patients with dengue fever (DF). Patients with DF had increased levels of TPO, compared with healthy individuals (p<0.005). Patients…

Interleukin-11 administration normalizes the platelet count in a hypersplenic cirrhotic patient.

We report the successful administration of interleukin-11 (IL-11 or oprelvekin), a promoter of megakaryocyte maturation, to a 54-year-old male Jehovah's Witness with hepatic cirrhosis and hypersplenic thrombocytopenia requiring surgery for symptomatic interstitial cystitis. This observation suggests that oprelvekin might be crucial in the acute management of certain types of hypersplenic thrombocytopenias.

Involvement of different second messengers in parathyroid hormone- and interleukin-1-induced interleukin-6 and interleukin-11 production in human bone marrow stromal cells.

Previous studies have suggested that increased secretion of bone active cytokines, such as interleukin-6 (IL-6) and interleukin-11 (IL-11), from osteoblasts and stromal cells play a pivotal role in the activation of osteoclasts and the genesis of osteoporosis. Various systemic and local factors can stimulate IL-6/IL-11 production, but the intracellular mechanism for such stimulation is largely unknown. In this study, we characterized the second messenger signaling in parathyroid hormone (PTH)- and IL-1-induced production of IL-6/IL-11 and studied the possible modulating effects of estrogen. rh…

Interleukin-11: A pivotal player and potential therapeutic target in prostate cancer.

Interleukin-11 (IL-11), a pleiotropic cytokine belonging to the interleukin-6 (IL-6) family, is implicated in the initiation and progression of various malignancies. Recent studies revealed that IL-11 plays multifaceted roles in prostate cancer, contributing to tumor cell proliferation, castration resistance, bone metastasis, and chemotherapeutic resistance. Interleukin-11 has emerged as a promising target for both diagnostic and therapeutic strategies. This review outlines the molecular structure and biological functions of IL-11; summarizes its role in early diagnosis, prognostic evaluation,…

Characterization of the angiomodulatory effects of Interleukin 11 cis- and trans-signaling in the retina.

BACKGROUND: The IL-6 cytokine family, with its crucial and pleiotropic intracellular signaling pathway STAT3, is a promising target for treating vasoproliferative retinal diseases. Previous research has shown that IL-6 cis-signaling (via membrane-bound receptors) and trans-signaling (via soluble receptors) can have distinct effects on target cells, leading to their application in various disease treatments. While IL-6 has been extensively studied, less is known about the angiogenic effects of IL-11, another member of the IL-6 family, in the retina. Therefore, the aim of this study was to chara

Effects of Designer Hyper-Interleukin 11 (H11) on Hematopoiesis in Myelosuppressed Mice.

The incidence of cancer is constantly increasing. Chemo/radiotherapy is one of major methods of treating cancer. Although adverse chemo/radiotherapy events, such as anemia and neutropenia, can be successfully cured, thrombocytopenia is still problematic. We constructed the Hyper-IL11 (H11) cytokine by linking soluble interleukin 11 receptor alpha (sIL-11Ralpha) with IL-11. In vivo H11 activity was examined in myelosuppressed mice. Myelosuppression was induced by either i) sublethal irradiation and carboplatin administration or ii) sublethal irradiation. A dose of 100 μg/kg of H11 or IL-11 was

Abnormal production of interleukin (IL)-11 and IL-8 in polycythaemia vera.

We studied the production of interleukin (IL)-11 and IL-8, two cytokines known to affect erythropoiesis, in polycythemia vera (PV). In vivo, IL-11 was detected more frequently in serum and bone marrow (BM) plasma of PV patients than in controls (healthy donors and patients with idiopathic erythrocytosis (IE)). In addition, serum IL-11 levels of PV patients were higher than those of controls. IL-8 was elevated in serum of both PV and IE patients (respective median levels: 38.6 and 242pg/ml, vs 4.4pg/ml for healthy donors). BM plasma IL-8 levels of PV patients (508pg/ml) were significantly highe

Interleukin-11 Signaling in Liver Disease: Mechanisms, Cellular Crosstalk, and Therapeutic Potential.

The liver has a remarkable regenerative capacity, but persistent injury caused by drugs, metabolic dysfunction, alcohol, and chronic inflammation can overwhelm this process and promote fibrosis and hepatocellular carcinoma. Interleukin-11 (IL-11), a cytokine that signals through glycoprotein 130 (gp130), was historically considered hepatoprotective; however, accumulating experimental evidence predominantly identifies endogenous IL-11 as an amplifier of liver injury and maladaptive repair. In hepatocytes, IL-11 promotes oxidative stress, mitochondrial dysfunction, and cell death while limiting …

Novel Interleukin-11 Inhibitors Attenuate Collagen Production in Patient-Derived Synovial Fibroblasts.

PURPOSE: Arthrofibrosis (AF), or excessive joint scarring, is a debilitating condition that causes pain and stiffness secondary to osteoarthritis and is often worsened by the surgical trauma of total knee arthroplasty (TKA). The underlying pathology involves dysregulated transforming growth factor-beta 1 (TGF-β1) signaling, which drives fibrogenesis. However, evidence from other organ systems suggests that interleukin-11 (IL-11) mediates fibrosis downstream of TGF-β1. This study examines the relationship between IL-11 and synovial fibrosis, a hallmark of AF, in patients with end-stage knee ost…

microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11.

BACKGROUND: Most patients with breast cancer in advanced stages of the disease suffer from bone metastases which lead to fractures and nerve … ast progenitor cells was verified in vitro. Dual-luciferase reporter assay was conducted to confirm Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in the prognosis of breast cancer patients with bone metastasis was determined by Kaplan-Meier analysis. RESULTS: Herein, we found that miR-124 was significantly reduced in metastatic bo …

Interleukin-6, interleukin-8, interleukin-11, and interferon-gamma levels in nasopharyngeal aspirates from wheezing children with respiratory syncytial virus or influenza A virus infection.

The differences between respiratory syncytial virus (RSV) and influenza A virus (IFAV) in the pathogenesis of wheezing in young children have not been clearly defined. The aim of this study was to assess the contributions of RSV vs IFAV in the pathogenesis of upper airway inflammation in wheezy young children. We compared interleukin (IL)-6, IL-8, IL-11, and interferon-gamma (IFN-gamma) levels in nasopharyngeal aspirates (NPA) from non-asthmatic children with respiratory virus infections (RSV in 17 children and IFAV in 13 children), asthmatic children with viral infections (RSV in nine childre

Evaluation of serum levels of interleukin-10, interleukin-11 and leukemia inhibitory factor in differentiation of eutopic and tubal ectopic pregnancies.

PURPOSE OF STUDY: To investigate whether serum levels of leukemia inhibitory factor (LIF), interleukin 10 (IL-10) and interleukin 11 (IL-11) are different in reference to the site of implantation. METHODS: Seventeen patients with laparoscopic diagnoses of tubal ectopic pregnancy (EP) and 19 patients with intrauterine pregnancy delivering healthy term neonates (IUP) were prospectively evaluated for LIF, IL-10 and IL-11 levels. The data were compared by using the Student's t-test, chi-square test, Kruskal-Wallis and the Mann-Whitney U test with Bonferroni's correction (p < 0.05) as appropriate.

Reduced expression of interleukin-11 and interleukin-6 in the periimplantation endometrium of excessive ovarian responders during in vitro fertilization treatment.

CONTEXT: Impaired implantation in assisted reproduction cycles with high serum estradiol (E2) concentrations may be related to abnormal endometrial functions. OBJECTIVE: The in vivo expression of T helper type 2 (Th2) cytokines in the periimplantation endometrium of infertile patients was compared between natural and stimulated cycles. INTERVENTIONS AND MAIN OUTCOME MEASURES: Uterine flushings and endometrial biopsies were collected 7 d after the LH surge in natural cycles or after human chorionic gonadotropin injection in stimulated cycles. Th2 cytokines were determined by immunolocalizatio

The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostatin M in rheumatoid arthritis.

OBJECTIVE: To determine the expression of interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OSM) and their major cellular sources in the joints of rheumatoid arthritis (RA) patients, as well as the correlation of circulating levels of these IL-6-type cytokines and C-reactive protein (CRP). METHODS: Messenger RNA (mRNA) and protein levels for IL-6, IL-11, LIF, and OSM were determined by using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: Cells isolated from the synovium of RA patients expressed mRNA

Interleukin 11-Induced MicroRNAs as Functional Mediators and Circulating Biomarkers of Cardiac Fibrosis.

BACKGROUND: Cardiac fibrosis can be triggered by several pathologies, including ischemic heart disease and aortic stenosis. Cardiac fibrosis is brought about by uncontrolled ECM (extracellular matrix) deposition by myofibroblasts. IL (interleukin)-11 (Il11) has been demonstrated as a trigger of multiorgan fibrosis. However, the molecular mechanisms underpinning IL-11-induced fibrosis require further characterization. Recent studies indicate that microRNA dysregulation contributes to the pathogenesis of cardiac fibrosis and can be targeted therapeutically. This study explored the hypothesis tha

Molecular characterization of the craniosynostosis-associated interleukin-11 receptor variants p.T306_S308dup and p.E364_V368del.

Interleukin-11 (IL-11) is a member of the IL-6 family of cytokines and is an important factor for bone homeostasis. IL-11 binds to and signals via the membrane-bound IL-11 receptor (IL-11R, classic signaling) or soluble forms of the IL-11R (sIL-11R, trans-signaling). Mutations in the IL11RA gene, which encodes the IL-11R, are associated with craniosynostosis, a human condition in which one or several of the sutures close prematurely, resulting in malformation of the skull. The biological mechanisms of how mutations within the IL-11R are linked to craniosynostosis are mostly unexplored. In this…

Interleukin 1 beta is induced by interleukin 11 during decidualization of human endometrial stromal cells, but is not released in a bioactive form.

Blastocyst implantation is dependent on the differentiation of endometrial stromal cells (ESC) into decidual cells. Decidualization of human ESC in vitro is enhanced by interleukin 11 (IL11), with associated changes in gene expression. Genes downstream of IL11 may provide targets for the treatment of implantation failure or the development of non-hormonal contraceptives. This study aimed to examine the effect of IL11 on interleukin 1 beta (IL1B) mRNA and protein expression during in vitro decidualization of ESC. Cells were decidualized with 17beta-estradiol and medroxyprogesterone acetate in t

Interleukin-11 signaling underlies fibrosis, parenchymal dysfunction, and chronic inflammation of the airway.

Interleukin (IL)-11 evolved as part of the innate immune response. In the human lung, IL-11 upregulation has been associated with viral infections and a range of fibroinflammatory diseases, including idiopathic pulmonary fibrosis. Transforming growth factor-beta (TGFβ) and other disease factors can initiate an autocrine loop of IL-11 signaling in pulmonary fibroblasts, which, in a largely ERK-dependent manner, triggers the translation of profibrotic proteins. Lung epithelial cells also express the IL-11 receptor and transition into a mesenchymal-like state in response to IL-11 exposure. In mic