IL6

Description
Interleukin-6 (IL-6) is a protein produced throughout the body as part of the immune response. IL-6 is one of a class of immune system regulators called cytokines that serve a variety of immune functions in response to acute illness or injury. As a pro-inflammatory cytokine, IL-6 is involved in activating inflammatory pathways. IL-6 is always present in the body in small amounts (<1-2 ug/mL), and concentration varies by time of day. However, in periods of immune activation, blood levels of IL-6 increase quickly, reaching as high as 40 times normal levels. IL-6 levels also rise with advancing age and are related to a variety of chronic conditions.

Significance of Measurement
Blood level of IL-6 is known to rise with advancing age in humans, and the dysregulation of IL-6 may be a contributing factor to many of the diseases of aging. Chronic conditions associated with high IL-6 include include osteoporosis, arthritis, type 2 diabetes, certain cancers, Alzheimer's disease (see Scholz, 1996; Papanicolaou, 1998). High levels of IL-6 are also related to cardiovascular disease, heart attack, and stroke (Kannel et al., 1987; Kuller et al., 1991, 1996; Mendall et al., 1996; Ridker et al., 1997; Tracy et al., 1995, 1997). In the elderly, high IL-6 levels result in an increased risk of functional disability and functional decline (Cohen et al., 1997; Ferrucci et al., 1999; Reuben et al., 2002), cognitive decline (Weaver et al., 2002), and mortality (Harris et al., 1999; Reuben et al., 2002).

The association of IL-6 with cardiovascular disease is related to the central role this cytokine plays in promoting the production of C-reactive protein (CRP), an important risk factor for myocardial infarction (Kiechl, et al., 2001; Ridker et al., 1997).

Method of Measurement
Blood serum sample is required. In the MacArthur Study an enzyme-linked immunosorbent assay (ELISA) test was used to measure interleukin-6 (IL-6) levels (High Sensitivity Quantikine kit, R&D Systems, Minneapolis, MN). In the Whitehall Study, IL-6 was assayed using a commercial high-sensitivity, 2-site, enzyme-linked immunosorbent assay kit.

References
· Cohen, H., Pieper, C., Harris, T., Rao, K.M., & Currie, M. (1997). Plasma IL-6: An indicator of functional disability in community dwelling elderly. Journal of Gerontology: Medical Sciences, 52A, M201-M208.
· Ferrucci, L., Harris, T.B., Guralnick, J.M., Tracy, R.P., Corti, M.C., Cohen, H.J., et al. (1999). Serum IL-6 level and the development of disability in older persons. Journal of the American Geriatrics Society, 47, 639-646.
· Harris, T.B., Ferrucci, L., Tracy, R.P., Corti, M.C., Wacholder, S., Ettinger, W.H. et al. (1999). Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. American Journal of Medicine, 106, 506-512.
· Kannel, W., Wolf, P., Castelli, W., & D’Agostino, R. (1987). Fibrinogen and risk of cardiovascular disease: The Framingham Study. Journal of the American Medical Association, 258, 1183-1186.
· Kiechl, S., Egger, G., Mayr, M., Wiedermann, C.J., Bonora, E., Oberhollenzer, F., et al. (2001). Chronic infections and the risk of carotid artherosclerosis: Prospective results from a large population study. Circulation, 103, 1064-1070.
· Kuller, L., Eichner, J., Orchard, T., Grandits, G., McCallum, L., & Tracy, R. (1991). The relation between serum albumin levels and risk of coronary heart disease in the Multiple Risk Factor Intervention Trial. American Journal of Epidemiology, 134, 1266-1277.
· Kuller, L., Tracy, R., Shaten, J., & Meilahn, E. (1996). Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. American Journal of Epidemiology, 144, 537-547.
· Mendall, M., Patel, P., Ballam, L., Strachan, D., & Northfield, T. (1996). C-reactive protein and its relation to cardiovascular risk factors: A population based cross sectional study. British Medical Journal, 312, 1049-1050.
· Papanicolaou, D.A., Wilder, R.L., Manolagas, S.C. & Chrousos, G.P. (1998). The pathophysiologic roles of interleukin-6 in human disease. Annals of Internal Medicine, 128, 127-137.
· Reuben, D.B., Cheh, A.I., Harris, T., Ferrucci, L., Rowe, J., Tracy, R., et al. (2002). Peripheral blood markers of inflammation predict mortality and functional decline in high-functioning community-dwelling older persons. Journal of the American Geriatrics Society, 50, 638-644.
· Ridker, P.M., Cushman, M., Stampfer, M.J., Tracy, R.P. & Hennekens, C.H. (1997). Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. The New England Journal of Medicine, 336, 973-979.
· Scholz, W. (1996). Interleukin 6 in diseases: Cause or cure? Immunopharmacology, 31, 131-150.
· Tracy, R., Bovill, E., Yanez, D., Psaty, B., Fried, L., Heiss, G., et al. (1995). Fibrinogen and factor VIII, but not fact VII, are associated with measures of subclinical cardiovascular disease in the elderly: Results from the Cardiovascular Health Study. Arteriosclerosis, Thrombosis and Vascular Biology, 15, 1269-1279.
· Tracy, R., Lemaitre, R., Psaty, B., Ives, D., Evans, R., Cushman, M., et al. (1997). Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: Results from the Cardiovascular Health Study and the Rural Health Promotion Project. Arteriosclerosis, Thrombosis and Vascular Biology, 17, 1121-1127.
· Weaver, J.D., Huang, M.H., Albert, M., Harris, T., Rowe, J.W., & Seeman, T.E. (2002). Interleukin-6 and risk of cognitive decline. Neurology, 59, 371-378.