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  • br Cytokine profile in MPN Results from

    2021-05-08


    Cytokine profile in MPN: Results from experimental investigation Cytokines are small molecules constituted by proteins or glycoproteins, which regulate the immune cell function and the immune system. They are secreted mainly by immune amitriptyline hydrochloride but also by other cells such as epithelial cells in response to all kinds of stimulation such as injury, infection and stress. They are considered mediators of inflammation and play critical roles in acute and chronic inflammation. In addition to the classically defined cytokines such as interleukins (ILs) and interferons (IFNs), there are a variety of other factors including tumor necrosis factors (TNFs), chemokines, colony stimulating factors (CSF), cell growth factors (TGF, HGF, PDGF and FGF), and angiogenic factors (such as VEGF) [30], [31]. The major immunomodulatory role of cytokines is the recruitment of immune effector cells to eradicate invasive stimuli. This process comprises transmission and feedback of information between the immune cell producing center and exertion of local activities that include angiogenesis, cell proliferation and cell migration. A balance in the cytokine network between pro-inflammatory and anti-inflammatory effects is required for effectively controlling normal function. Otherwise, its dysregulation could generate organ disorders or even diseases. Dysregulation of cytokine networks has been reported in MPN [21]. Cytokines evaluated in 15 MPN studies (literature from 1997 to 2018) are summarized in Table 1. Cytokine evaluation in MPN dates back to 1997. Early studies have evaluated limited subtypes of cytokines because of technology limitations or kit restrictions. Now with the application of multiplex cytokine assays, a panel of cytokines can be measured per sample at the same time and can provide more complete information of the cytokine profile in MPN patients. As indicated in Table 1, about 79 kinds of cytokines have been evaluated at least once [32]. Due to limited sample numbers, it is difficult to make a concise conclusion for all the cytokines. However, several cytokines among these have been frequently evaluated in different studies, and further correlative analysis indicates that 12 of the 79 cytokines could be prognostic factors for MPN patients. The 12 cytokines are IL-1α, IL-1β, IL-2Ra, IL-6, IL-8, IL-11, IFN, TNF-α, TGF-β, VEGF, PDGF and MIP-1. Therefore, we focus on these 12 cytokines in this review.
    Conclusions
    Conflict of interest
    Funding statement This work was supported by the National Natural Science Foundation of China (NSFC) [Grant number 81670125, 2016].
    Therapeutic Potential of Synthetic Cytokine Signaling Cytokines and growth factors, which comprise more than 100 protein mediators can be subdivided into groups including growth, death, and survival factors, interleukins (ILs), interferons (IFNs), and chemokines. Cytokines signal via three different types of transmembrane receptors, receptor tyrosine kinases, receptors with associated kinases (see Glossary), amitriptyline hydrochloride and G-protein-coupled receptors. They are directly secreted as either soluble or membrane-bound proteins, which can be released by ectodomain shedding [1]. Cytokines and their molecular components of signal transduction are key players in health and disease. Today, a variety of diseases are targeted by cytokine-based hormone therapy, including insulin, growth hormone (GH), erythropoietin (EPO), thrombopoietin (TPO), granulocyte colony-stimulating factor (G-CSF), IFNs, IL-2, and IL-11 [2]. Yet, abnormal activation of cytokine signaling by excessive cytokine production or hyperactive mutated receptors frequently results in life-threatening diseases including chronic inflammatory diseases and cancer. A basic understanding of the underlying molecular principles of receptor activation established in the early 1990s has enabled the development of targeted therapeutics, including abrogated signaling of tumor necrosis factor (TNF), IL-6, and many others [3]. The majority of such inhibitors, namely monoclonal antibodies or small molecules, target cytokine/cytokine receptor binding interfaces or receptor (-associated) kinases.