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Preformulation of New Biological Entities
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
Riccardo Torosantucci, Vasco Filipe, Jonathan Kingsbury, Atul Saluja, Yatin Gokarn
Cytokines are small hormone proteins that act in cell signaling pathways, most commonly in the activation of immune system components such as lymphocytes and macrophages. Interferons are potent glycoprotein cytokines with antiviral properties and can suppress uncontrolled cell proliferation. They have been used in the treatment of multiple sclerosis, immunological cancers, and hepatitis. Biotherapeutic interferons include interferon-α (e.g., Roferon-A®, Intron-A®, and Alferon-N®), interferon-β (e.g., Avonex®, Betaseron®, and Extavia®), and interferon-γ (e.g., Actimmune®). Similar to the interferons, the interleukins function as biochemical signals during immune response, with either stimulatory or inhibitory activities. For example, interleukin-1 (IL-1) controls pro-inflammatory reactions in response to tissue injury by pathogen- or danger-associated molecular patterns. Therefore, IL-1 receptor antagonists, such as anakinra (Kineret®), can be used in the treatment of inflammatory conditions such as rheumatoid arthritis. Recombinant interleukin-2 (IL-2), aldesleukin (Proleukin®), stimulates T cells and is used in the treatment of metastatic renal cell carcinoma and melanoma.
Wound Healing and Inflammatory Response to Biomaterials
Published in Chih-Chang Chu, J. Anthony von Fraunhofer, Howard P. Greisler, Wound Closure Biomaterials and Devices, 2018
P. H. Lin, M. K. Hirko, J. A. von Fraunhofer, H. P. Greisler
During the process of adhesion to, and/or phagocytosis of, biomaterials and their degradation products, macrophages become activated. Macrophage activation leads to release of bioactive agents, which have the potential to either degrade the biomaterial or compromise its functional capacity. In examining biological activity, it has been shown that macrophages are capable of producing a variety of growth factors, cytokines, chemotactic agents, proteases, arachidonic acid metabolites, oxygen-free radicals, complement components, and coagulation factors (Table 2.5). These secreted products may have a wide spectrum of effects from cell proliferation to cell death, and contribute to the chronic inflammatory response. IL-1, for instance, is a regulatory protein produced by macrophages, which has multiple effects on both the inflammatory and immune responses.49 IL-1 is an important mediator of the inflammatory process because of its regulation of fibroblast growth, proliferation, and protein synthesis. By stimulating fibroblast activity, IL-1 induces the synthesis of the fibroblast product collagen,50–52 and has also been shown to induce the proliferation of endothelial and smooth muscle cells.49,53,54 These bioactive characteristics of IL-1 also indicate its importance as a biological mediator in terms of the biocompatibility of implanted materials.
Enzyme Catalysis
Published in Harvey W. Blanch, Douglas S. Clark, Biochemical Engineering, 1997
Harvey W. Blanch, Douglas S. Clark
The interleukins are a large subfamily of cytokines, comprising at least 10 types. They function as regulators of the immune response and bind to receptors at various cell surfaces, where they modulate immunological activity. IL-2 plays a key role in immune functioning, and is produced by T lymphocytes when activated by an antigen or mitogen. It stimulates growth and differentiation of T and B lymphocytes, and controls the activity of natural killer cells. Its function is thus key to both cell-mediated and humoral immunity. IL-2 has a molecular weight of 15,500Da, and contains one intrachain disulphide linkage. The protein is arranged in four antiparallel α-helical regions. It is produced in E. coli in an unglycosylated form, but retains its biological activity. It has been used to treat several forms of cancer and infectious diseases, including AIDS. IL-1 is naturally produced by phagocytic cells and it elicits a variety of responses, including proliferation of thrombocytes, fibroblasts and lymphocytes. It also promotes wound healing. It is produced in recombinant E. coli.
Risk modelling further implicates the angiogenesis pathway in anterior cruciate ligament ruptures
Published in European Journal of Sport Science, 2022
Masouda Rahim, Miguel Lacerda, Malcolm Collins, Michael Posthumus, Alison V. September
Interleukin-1, is involved in a variety of cellular activities, including cell proliferation and differentiation, angiogenesis and apoptosis. In particular, IL-1β, encoded by the IL1B gene, is a pro-inflammatory cytokine responsible for activating numerous downstream signalling cascades (Thampatty et al., 2007; Yang et al., 2005). IL-6, encoded by IL6, is a pleiotropic cytokine with both pro-inflammatory and anti-inflammatory effects. It acts on a wide range of tissues with roles in apoptosis, cell growth and differentiation, as well as angiogenesis. Elevated IL-6 expression was reported in tissues that undergo angiogenesis and IL-6 was also shown to induce VEGF levels to a similar degree as has been observed in hypoxic states (Cohen et al., 1996). IL-6 exerts its biological effects by binding and forming a complex with the interleukin-6 receptor (IL6R) and therefore the receptor may also play a necessary role in IL-6 induced angiogenesis.
Low-dose cadmium exposure exacerbates polyhexamethylene guanidine-induced lung fibrosis in mice
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Min-Seok Kim, Sung-Hwan Kim, Doin Jeon, Hyeon-Young Kim, Jin-Young Han, Bumseok Kim, Kyuhong Lee
Inflammatory cytokines are released by various cells, mainly inflammatory cells, and are associated with fibrosis development (Borthwick, Wynn, and Fisher 2013; Piguet et al., 1989; Zhang et al. 2017). Numerous inflammatory mediators and cytokines are present in BALF and lung specimens of patients with IPF (Bringardner et al. 2008). Similarly, previous results demonstrated elevated expression of various inflammatory cytokines in BALF and lung tissues of PHMG-treated mice (Kim et al. 2018; Lee et al. 2016b; Song et al. 2014). Cd functions as an activator of transcription factors, such as activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB), which are involved in the synthesis of various inflammatory mediators (Låg et al. 2010). Our findings showed that expression of IL-1β, CCL6, and CCL17 increased in pulmonary tissues of mice in the PHMG + CdCl2 compared with PHMG alone (Figure 5). IL-1β is a major cytokine involved in the initiation and persistence of inflammation. Induction of IL-1β expression in mouse lungs induces pulmonary inflammation through neutrophil and macrophage infiltration (Dinarello 1996; Lappalainen et al. 2005). Recently Kim et al. (2018) noted that CCL6 and CCL17 levels were significantly increased in lungs of PHMG- and BLM-treated mice. CCL6 plays critical roles in the pathogenesis of IL-13-induced pulmonary inflammation and tissue remodeling (Ma et al. 2004). The expression of CCL17 rose following BLM-induced pulmonary fibrosis and in IPF lung tissue specimens (Belperio et al. 2004). Data suggest that Cd enhances the expression of inflammatory cytokines in pulmonary tissue of animals treated with PHMG.