Congenital Causes of Erythrocytosis/Polycythemias and Thrombocytosis
Richard T. Silver, Ayalew Tefferi in Myeloproliferative Disorders, 2007
Although Tpo is the most potent regulator of megakaryopoiesis and platelet production, other cytokines and growth factors have also been described to have stimulatory effects. Interleukin-11 (IL-11) is a pleiotropic cytokine originally isolated from bone marrow stromal cells, which promotes megakaryocyte differentiation in vitro and results in increased platelet counts in vivo (41). IL-11 has been shown to shorten thrombocytopenia in patients undergoing chemotherapy and has been approved for this indication (42,43). Other cytokines with megakaryocyte stimulatory activity that have been tested for clinical applications are IL-3 and IL-6 (44). However, due to limited effectiveness and considerable side effects, these cytokines are not used for clinical purposes. Clinical trials with Tpo for the treatment of thrombocytopenia have been stopped because of the occurrence of neutralizing antibodies that caused severe thrombocytopenia (45,46). Recently, AMG531, a Tpo peptide agonist engineered into a recombinant immunoglobulin protein, has been shown to increase platelet levels in patients with idiopathic thrombocytopenia without causing significant adverse effects (47). This and other Tpo-mimetic compounds under development hold promise to become available for the treatment of patients with thrombocytopenia (48).
Interleukin 6: Role in the Pathogenesis of Cancer
Thomas F. Kresina in Immune Modulating Agents, 2020
The gene for IL-6 has been cloned and sequenced, and its structure described [17]. It is a 15- to 30-kDa glycoprotein, consisting of 212 amino acids, based on a sequence deduced from cloned IL-6 copy deoxyribonucleic acid (cDNA) [4–7,17]. It is differentially modified by glycosylation, resulting in the range of molecular weights seen for this cytokine. The gene for IL-6 in humans is on chromosome 7; it consists of 5 exons and 4 introns, with the same exon/intron pattern as the gene for granulocyte colony-stimulating factor (G-CSF) [4–7], There is some amino acid sequence similarity between IL-6 and G-CSF, suggesting that there may be some similarity in the tertiary structure of these molecules. Also, IL-6 appears to be related to various other defined cytokines, including oncostatin M (OsM), interleukin 11 (IL-11), ciliary neurotrophic growth factor (CNTF), and leukemia inhibitory factor (LIF) [7,18]. Therefore, IL-6, along with various other cytokines, appears to belong to a family of related IL-6-like cytokines [6,7].
Micronutrients in Improvement of the Standard Therapy in Cancer
Kedar N. Prasad in Micronutrients in Health and Disease, 2019
Breast cancer cells (MDA-MB-231 and MCF-7) and tissues have lower expression of miR-137, miR-15a, and miR-16 but have higher levels of their respective proteins EFF-α, CCNE, and cyclin D and Bcl2 than noncancerous cells and tissues. Overexpression of these microRNAs inhibited their respective target proteins, and reduced the growth, migration, and invasion of tumor cells in culture and induced apoptosis.22–24 Normal breast epithelial cells have elevated expression of miR-135 and miR-203 and undetectable levels of its target protein Runx2 (runt-related transcriptional factor-2). Overexpression of these microRNAs in MDA-MB-231-luv cells reduced the tumor growth and bone metastasis by reducing the levels of Runx2-regulated IL-11 (interleukin-11), MMP-13 (Matrix metallopeptidase-13), and PTHrP (parathyroid hormone-related peptide).25 Thus, elevated expression of miR-137, miR-15a, miR-16, miR-135, and miR-203 may act as tumor suppressors. The results are summarized in Table 8.2.
Interleukin-11 Overexpression and M2 Macrophage Density are Associated with Angiogenic Activity in Proliferative Diabetic Retinopathy
Published in Ocular Immunology and Inflammation, 2020
Ahmed M. Abu El-Asrar, Ajmal Ahmad, Eef Allegaert, Mohammad Mairaj Siddiquei, Priscilla W. Gikandi, Gert De Hertogh, Ghislain Opdenakker
Interleukin-11 (IL-11) is a multifunctional member of the IL-6 family of cytokines which include cytokines that share the use of the glycoprotein-130 (gp130) receptor β-subunit signaling pathway. The engagement of the gp130 receptor induces the activation of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway.11,12 Signaling by IL-11 proceeds via an interaction of the protein with its membrane-specific receptor IL-11Rα and a subsequent interaction of the complex with the transmembrane signal-transducing receptor gp130.13 IL-11 has been strongly implicated as a proinflammatory and proangiogenic cytokine in the pathogenesis of various inflammation-associated cancers of epithelial cell origin14–18 as well as in autoimmune and inflammatory diseases.19–21
The safety and efficacy of interleukin 11 for radiation injury
Published in Expert Opinion on Drug Safety, 2023
Interleukin 11 (IL-11) is a member of the IL-6 family with several, well-documented modes of biological action, namely and most notably, stimulatory and maturational actions on megakaryocytopoiesis within hematopoietic tissues and related thrombocytopoiesis, along with anti-inflammatory and cytoprotective effects on both gastrointestinal (GI) crypts and hematopoietic progenitors [1]. IL-11 belongs to the gp130 family of cytokines and besides IL-6, IL-11 is the only member of this family which acts on a homodimer of the ubiquitously expressed gp130 co-receptor. Responsiveness of cells is, therefore, determined by the presence of the IL-11 receptor (the IL-6 receptor in the case of IL-6). It might be possible that certain cells are not responsive to IL-11 due to the lack of the IL-11 receptor expression. In such a case, the use of a ‘Hyper-IL-11’ (soluble IL-11 receptor-α fused with IL-11 without any artificial linker to avoid induction of antibody production) might be not only possible but perhaps appropriate [2].
MEK/ERK/RUNX2 Pathway-Mediated IL-11 Autocrine Promotes the Activation of Müller Glial Cells during Diabetic Retinopathy
Published in Current Eye Research, 2022
Na Ji, Yang Guo, Songbai Liu, Manhui Zhu, Yuanyuan Tu, Jiahui Du, Xiaoxiao Wang, Ying Wang, E. Song
Circular RNA-ZRANB1 (cZRANB1) acts as a miRNA sponge to regulate the functions of MGCs through cZRANB1/microRNA-217 (miR-217)/Runt-related transcription factor 2 (RUNX2) network,8 indicating that RUNX2 is located in MGCs. As a transcript factor, RUNX2 regulates the transcription of multiple target genes, including Interleukin-11 (IL-11).9 IL-11, the number of interleukin-6 (IL-6) cytokine family, is secreted by MGCs10 that constitutively express the receptor of IL-11, which is named as interleukin 11 receptor subunit alpha (IL-11RA).11 IL-11 promotes the activation of primary human fibroblasts in response to transforming growth factor β1 (TGFβ1) exposure.12 Therefore, we speculated that IL-11 binding to IL-11RA on MGCs could form an autocrine loop to facilitate Müller glial cell (MGC) activation.