CORPLEX™ HUMAN CYTOKINE PANEL 2

IL-1β

Interleukin-1 beta (IL-1β, catabolin) is a 269 aa cytokine (31 kDa), produced by activated macrophages which is proteolytically processed to its active form by caspase-1. IL-1β is an important mediator of the inflammatory response involved in a variety of cellular activities including cell proliferation, differentiation, apoptosis and autoinflammatory diseases. Monocytes from patients with autoinflammatory syndromes release more processed IL-1β than cells from healthy subjects suggesting that it is involved in inflammation of 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-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 22- 28kD phosphorylated and variably glycosylated molecule. Mature human IL-6 is 183 amino acids (aa) in length. 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 anti-inflammatory 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.