||Interleukin 6 (IL-6) is a pleiotropic a-helical 22-28 kDa phosphorylated and variably glycosylated (1-5) cytokine. Mature human IL-6 is 183 amino acids (aa) in length and shares 41% aa sequence identity with mouse and rat IL-6 (6). Alternate splicing generates several isoforms with internal deletions, some of which exhibit antagonistic properties (7-10). Cells known to express IL-6 include CD8+ T cells, fibroblasts, synoviocytes, adipocytes, osteoblasts, megakaryocytes, endothelial cells (under the influence of endothelins), sympathetic neurons, cerebral cortex neurons, adrenal medulla chromaffin cells, retinal pigment cells, mast cells, keratinocytes, Langerhans cells, fetal and adult astrocytes, neutrophils, monocytes, eosinophils, colonic epithelial cells, B1 B cells, and pancreatic islet beta cells (2, 7, 10-33). IL-6 production is generally correlated with cell activation and is normally kept in control by glucocorticoids, catecholamines and secondary sex steroids (2). Normal human circulating IL-6 is in the 1 pg/mL range, with slight elevations during the menstrual cycle, modest elevations in certain cancers, and large elevations after surgery (34-38).IL-6 induces signaling through a cell surface heterodimeric receptor complex composed of a ligand binding subunit (IL-6 R) and a signal transducing subunit (gp130). IL-6 binds to IL-6 R, triggering IL-6 R association with gp130 and gp130 dimerization (39). gp130 is also a component of the receptors for CLC, CNTF, CT-1, IL-11, IL-27, LIF, and OSM (40). Soluble forms of IL-6 R are generated by both alternate splicing and proteolytic cleavage (3). In a mechanism known as trans-signaling, complexes of soluble IL-6 and IL-6 R elicit responses from gp130-expressing cells that lack cell surface IL-6 R (1, 3). Trans-signaling enables a wider range of cell types to respond to IL-6, as the expression of gp130 is ubiquitous, while that of IL-6 R is predominantly restricted to hepatocytes, monocytes, and resting lymphocytes (1-3). Soluble splice forms of gp130 block trans-signaling from IL-6/IL-6 R but not from other cytokines that use gp130 as a co-receptor (3, 41).IL-6, along with TNF-a and IL-1, drives the acute inflammatory response, is almost solely responsible for fever and the acute phase response in the liver, and is important in the transition from acute inflammation to either acquired immunity or chronic inflammatory disease (1-4). It contributes to chronic inflammation in conditions such as obesity, insulin resistance, inflammatory bowel disease, inflammatory arthritis, and sepsis when dysregulated, often involving IL-6 trans-signaling (1, 2). It plays an important role in differentiation of naïve T cells to Th17 inflammatory cells in the presence of TGF-b. IL-6 modulates bone resorption and is a major effector in inflammatory joint destruction in rheumatoid arthritis through promoting Th17 T cell activity (1). It contributes to atherosclerotic plaque development and destabilization (2). IL-6 can also have anti-inflammatory effects, however, such as in skeletal muscle where it is secreted in response to exercise (2). It promotes hematopoiesis by being a growth factor for hematopoietic stem cells, induces B cell maturation to plasma cells, and perpetuates multiple myeloma (1, 42). IL-6 also promotes, but probably does not initiate, other types of inflammation-associated carcinogenesis, such as colitis-associated cancer (1). The Quantikine HS Human IL-6 Immunoassay is a 5.5 hour solid-phase ELISA designed to measure human IL-6 in serum, plasma, and urine. It contains E. coli-expressed recombinant human IL-6 and has been shown to accurately quantitate the recombinant factor. Results obtained using natural human IL-6 showed linear curves that were parallel to the standard curves obtained using the Quantikine HS kit standards. These results indicate that this kit can be used to determine relative mass values for naturally occurring human BAFF.alues for naturally occurring IL-6.