IL-1β- Interleukin-1 beta (IL-1β), also known as catabolin, is a cytokine of 269 amino acids (molecular weight 31 kDa). This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase-1. IL-1β is an important mediator of the inflammatory response and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. IL-1β is the most studied member of the IL-1 family of cytokines due to its role in mediating autoinflammatory diseases. Blood monocytes from patients with autoinflammatory syndromes release more processed IL-1β than cells from healthy subjects and thus likely account for the inflammation in these diseases.Neutralization of IL-1β results in rapid and sustained reduction in disease severity. Although some autoinflammatory diseases are due to gain-of-function mutations for caspase-1 activity, common diseases such as gout, type 2 diabetes, heart failure, recurrent pericarditis, rheumatoid arthritis, and smouldering myeloma are also responsive to IL-1β neutralization.
IL-2 - Interleukin 2 (IL-2) is an alpha-helical cytokine of 153 amino acids (molecular weight 17.6kDa) whose primary role is regulation of activities of lymphocytes that are responsible for immunity. During infection, the binding of antigens to T cell receptors trigger secretion of IL-2 and expression of IL-2 receptors (IL-2R), promoting the growth, proliferation, and differentiation of T cells to become effector T cells. IL2/IL2R interaction stimulates growth and differentiation of antigen-specific CD4+ and CD8+ T cells, resulting in immunologic memory of the antigens. IL-2 is also responsible for discrimination between foreign ("non-self") and "self", and as such is a target of immunosuppressive regimens which inhibit the production of IL-2 by antigen-activated T cells and block IL-2R signaling, preventing the clonal expansion and function of antigen-selected T cells.
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-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-12 P70 - 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.
TNFα - Mouse 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. Mouse 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.