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Inflammation, ischemia, and reperfusion are important mechanisms involved in pandemics and trauma.
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Cytokine storm is an over-exaggerated inflammatory response with infectious and non-infectious causes.1,2 The concept first appeared with graft versus host disease and then with cytomegalovirus, Epstein-bar virus associate hemophagocytic lymphohistiocytosis, group A streptococcus, influenza virus, variola virus, avian H5N1 influenza virus, and severe acute respiratory distress syndrome.3–8 It has also been associated with use of muromonab-CD3 (OKTS), Coley’s toxins, genetic diseases such as inappropriate inflammasome activation or idiopathic multicentric Castleman’s disease, CAR T-cell therapy, hemophagocytic lymphohistiocytosis, and most recently SARS-CoV-2 infection.2 There is no single definition of cytokine storm or cytokine release syndrome that is universally accepted.2
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Cytokines are proteins with roles on intracellular signaling for communication1 (Table 3-1 to 3-3). They are produced by cells of the innate immune system such as neutrophils, monocytes, and macrophages.2 Neutrophils also produce extracellular traps and fibers that contribute to thrombi formation.2 Macrophages’ other roles include removal of senescent cells, antigen presentation, immune-regulation, and tissue repair.2 NK cells have cytolytic roles.2 The major types of cytokines include interferons, which regulate innate immunity with antiviral and anti-proliferative properties; interleukins, which may be pro-inflammatory or anti-inflammatory and growth of leukocytes; chemokines, which are generally pro-inflammatory for chemotaxis and leukocyte recruitment; colony-stimulating factors for hematopoietic progenitor cell proliferation and differentiation; and tumor necrosis factor, which activates cytotoxic T lymphocytes1 The magnitude of chemokine and cytokine expression are related to pathogen-associated molecular patterns (PAMP).1
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