CORPLEX™ CYTOKINE PANEL (IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-22, TNFα)
IFN-γ
Human interferon-gamma (IFN-γ) is a dimeric cytokine with subunits of 146 amino acids. Mature human IFN-γ exists as a non-covalently linked homodimer of 20-25 kDa variably glycosylated subunits. IFN-γ does not display significant homology with the other two interferons, IFN-alpha and IFN-beta. Murine and human IFN-γ show approximately 40% sequence homology at the protein level. IFN-γ is expressed by Th1 cells, Tc cells, dendritic cells and natural killer cells, especially under inflammation conditions. IFN-γ binds to its heterodimeric receptor IFN-γR and related complex for biological function. It plays a key role in host defense by promoting the development and activation of Th1 cells, chemoattraction and activation of monocytes and macrophages, upregulation of antigen presentation molecules, and immunoglobulin class switching in B cells. In addition, IFN-γ functions as an anti-inflammatory mediator by promoting the development of regulatory T cells and inhibiting Th17 cell differentiation. It also exhibits antiviral, antiproliferative, and apoptotic effects. IFN-γ is also an attractive drug target for immuno-regulatory diseases.
IL-10
Interleukin 10 (IL-10) is an alpha-helical, homodimeric cytokine, each subunit composed of 178 amino acids (18 kDa). The major role of IL-10 is to act as an antiinflammatory cytokine. It is produced primarily by monocytes, type 2 T helper cells and B cells. IL-10 is also released by cytotoxic T cells to inhibit the action of natural killer cells during the immune response to viral infection. It has multiple effects in immunoregulation and inflammation, including down regulation of Th1 cytokine expression, MHC class II antigens, and stimulatory molecules on macrophages. IL-10 can also inhibit synthesis of pro-inflammatory cytokines such as IFN-g, IL-2, TNFa and GM-CSF made by macrophages and regulatory T cells. IL-10 is among cytokines secreted by muscle cells, whose elevation during physical activity suggests that exercise promotes an environment of anti-inflammatory cytokines. IL-10 has garnered interest as a potential anti-inflammatory therapeutic, but initial studies with rheumatoid arthritis have shown limited efficacy.
IL-4
Human Interleukin-4 (IL-4) is a monomeric cytokine, approximately 13-18 kDa, expressed by Th2-biased CD4+ T cells, mast cells, basophils, and eosinophils. IL-4 has a compact, globular fold (similar to other cytokines) stabilized by 3 disulphide bonds. Mature human IL-4 shares 55%, 39%, and 43% amino acid sequence identity with bovine, mouse, and rat IL-4, respectively. By binding to IL-4 receptor or receptor complex, IL-4 has many biological functions. It promotes cell proliferation, survival, and immunoglobulin class switch to IgG4 and IgE in human B cells, acquisition of the Th2 phenotype by naïve CD4+ T cells, priming and chemotaxis of mast cells, eosinophils, and basophils, and the proliferation and activation of epithelial cells. IL-4 plays an important role in the development of allergic inflammation and asthma.
IL-5
Interleukin 5 (IL-5) is a cytokine which is predominantly associated with antigen-induced eosinophilia. The activation of T Helper 2 (Th2) cells leads to the production of IL-5. IL-5 consists of two identical polypeptide chains composed of 115 amino acids (molecular weight 45kDa). Several studies correlate higher levels of IL-5 with inflammatory disorders such as angioedema, eosinophilia, multiple sclerosis, persistent asthma, and cow’s milk allergy in newborn infants.
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 human IL-6 is 183 amino acids (aa) in length and shares 41% aa sequence identity with mouse 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. Because of its role in inducing inflammation and auto-immune 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.
IL-10
Interleukin 10 (IL-10) is an alpha-helical, homodimeric cytokine, each subunit composed of 178 amino acids (18 kDa). The major role of IL-10 is to act as an antiinflammatory cytokine. It is produced primarily by monocytes, type 2 T helper cells and B cells. IL-10 is also released by cytotoxic T cells to inhibit the action of natural killer cells during the immune response to viral infection. It has multiple effects in immunoregulation and inflammation, including down regulation of Th1 cytokine expression, MHC class II antigens, and stimulatory molecules on macrophages. IL-10 can also inhibit synthesis of pro-inflammatory cytokines such as IFN-g, IL-2, TNFa and GM-CSF made by macrophages and regulatory T cells. IL-10 is among cytokines secreted by muscle cells, whose elevation during physical activity suggests that exercise promotes an environment of anti-inflammatory cytokines. IL-10 has garnered interest as a potential anti-inflammatory therapeutic, but initial studies with rheumatoid arthritis have shown limited efficacy.
IL-12p70
Interleukin-12, p70 (IL-12 p70) is a disulfide-linked heterodimeric 70-kDa cytokine composed of a 197 amino acid 35-kDA (p35) subunit and a 306 amino acid 40-kDa (p40) subunit. It is naturally produced by dendritic cells, macrophages and human B-lymphoblastoid cells in response to antigenic stimulation. IL-12 stimulates growth and function of T cells, production of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) from T cells and natural killer (NK) cells, and reduces IL-4-mediated suppression of IFN-γ. IL-12 has been reported to be associated with autoimmune and inflammatory conditions. Increased IL-12 plasma levels may also be detected in patients with neurological disorders such as multiple sclerosis.
IL-22
IL-22 is a member of the IL-10 superfamily of cytokines. These cytokines are pleiotropic, affecting a wide range of immune functions. IL-22 is produced by Dendritic, T, and Innate Lymphoid cells and can be found in a wide range of tissues. Biological activity of IL-22 is initiated through interactions with IL-22R1 and IL-10R2, as well as IL-22BP1 and is regulated by IL-17A. IL-22 activation plays a role in the initiation and regulation of nonspecific immune response. IL-22 is associated with psoriasis; serum levels of the cytokine correlate with the severity of the disease. Emerging evidence suggests that IL-22 can play a role in other autoimmune disorders such as Inflammatory Bowel Disease, Rheumatoid Arthritis, and Multiple Sclerosis, perhaps due to its role in inflammatory responses, which are regulated by IL-17A. IL-22 has also been implicated as a Reg gene regulator promoting β-cell production in Type 1 diabetes. The Total IL-22 Discovery assay detects free IL-22 and IL-22 bound to IL-22BP.
TNFα
Human tumor necrosis factor alpha (TNFα) is a homotrimeric transmembrane protein that functions as a proinflammatory cytokine. It is produced mainly by macrophages but also by a variety of other cell types, including monocytes, neutrophils, and T-cells. 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. Human TNFα is a non-glycosylated protein of 157 amino acids, with a molecular weight of approximately 17,000 daltons. The clinical relevance of TNFα stems from its association with numerous disease states including rheumatoid arthritis, cancer, cachexia, and Crohn’s disease.