IFN-γ - Interferon-gamma (IFNγ), exerts a wide range of immunoregulatory activities Mature mouse IFN-gamma exists as a noncovalently linked homodimer of 20-25 kDa variably glycosylated subunits. IFNγ binds IFN-γ receptors (IFNγ R1 and IFNγ R2), which are expressed on most immune cells, to activate the JAK-STAT pathway. IFNγinduced signaling increases the expression of class 1 major histocompatibility complex (MHC) molecules. IFNγ is produced by a variety of immune cells under inflammatory conditions, notably by T cells and NK cells. It plays a key role in host defense by promoting the development and activation of Th1 cells, chemoattraction and activation of monocytes and macrophages, and up-regulation of antigen presentation molecules. It also exhibits antiviral, antiproliferative, and apoptotic effects.
IL-1β - The IL-1 family consists primarily of three proteins: IL-1α, IL-1β (agonists) and IL-1ra (antagonist) which interact with the IL-1 receptor. IL-1β shares 33% homology with IL-1α. IL-1β exists as a 33 kDa precursor which is cleaved by caspase-1 into its 17 kDA active form. It is unknown how IL-1β is actively secreted but it is suggested exocytosis, transport by multi-drug resistance transporters, and cell death may all play a role. Knockout models of IL-1β show no gross physiological detriment, though its role is suspected to function in disease states rather than healthy tissue. Evidence shows potential involvement in Long Term Potentiation demonstrating increases following induction, and the prevention of induction with a competitive antagonist. IL-1β is believed to be part of an inflammatory response thought to be protective to insult and injury but often goes awry. There is a distinguishable link between oxidative stress, glutamate excitotoxicity and IL-1β.
IL-6 - Interleukin 6 (IL-6) is an alpha-helical cytokine with a wide variety of biological functions, including inducement of acute phase reactions, inflammation, hematopoiesis, bone metabolism, and cancer progression. It is secreted by multiple cell types as a 22k-28k dalton phosphorylated and variably glycosylated molecule. Mature mouse IL-6 shares 41% aa sequence identity with human and rat IL-6. IL-6 is secreted by T cells and macrophages to induce immune responses following tissue trauma leading to inflammation. IL-6 also acts as an anti-inflammatory myokine, secreted by muscles during contraction after which it acts to increase breakdown of fats and improve insulin resistance.3 Because of its role in inducing inflammation and autoimmune response, there is interest in developing anti-IL-6 agents as potential therapies against various diseases, including rheumatoid arthritis and cancer.
IL-8 - Interleukin 8 (IL-8) is a cytokine of 72 amino acids (molecular weight 8 kDa) whose primary role is induction of chemotaxis in neutrophils, basophils, and T-cells, causing them to migrate to the site of infection. IL-8 also induces phagocytosis by the target cells. IL-8 is secreted by cells involved in the immune response to antigens, typically starting with macrophages, which release IL-8 to recruit other cells. Secretion of IL-8 is increased by oxidant stress, which thereby cause the recruitment of inflammatory cells, inducing a further increase in oxidant stress mediators, making it a key parameter in localized inflammation. IL-8 elevation has been associated with a range of clinical conditions, including psoriasis, chronic hepatitis C, and thyroid disease. IL-8 has recently been identified as a potential therapeutic target in inflammatory diseases.
TNF-α - Tumor Necrosis Factor alpha (TNFα) is a polypeptide cytokine produced by monocytes and macrophages. The involvement of TNFα in several signal transduction pathways links the protein to such diverse functions as acute inflammation, apoptosis, septic shock, cellular proliferation, and differentiation. The clinical relevance of TNFα is from its association with numerous disease states including rheumatoid arthritis, cancer, cachexia, and Crohn’s disease.