Minireview - interleukin 6.docVIP

Minireviews Interleukin 6 Date 1/1/1999 First printed in RD Systems 1999 Catalog. Overview While a number of Interleukins such as Interleukin-1 (IL-1)1 and IL-102 are seemingly pleiotrophic in their effects, Interleukin 6 (IL-6) may be considered the prototypic pleiotrophic cytokine.3, 4 This is reflected in the variety of names originally assigned to IL-6 based on function, including Interferon beta 2, IL-1-inducible 26 kD Protein, Hepatocyte Stimulating Factor, Cytotoxic T-cell Differentiation Factor, B cell Differentiation Factor (BCDF) and/or B cell Stimulatory Factor 2 (BSF2).3 Once all the activities associated with the various names for IL-6 became connected with one common gene, the actual name IL-6 was proposed for this molecule.5 A number of cytokines make up an IL-6 cytokine family. Membership in this family is based on a helical cytokine structure and receptor subunit makeup.6, 7 For reviews on IL-6, see references 3, 4, 8-11. Figure 1. IL-6 and Acute Phase Proteins. SAA = Serum Amyloid Protein A. CRP = C-Reactive Protein. Structural Information Human IL-6 is a variably glycosylated, 22-27 kDa secreted glycoprotein that serves as a prototype for a family of molecules that includes leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1) and IL-11. Although all molecules possess a similar helical structure, their association is due to their functional redundancy and receptor interactions.3, 6, 7, 11 IL-6 is translated as a 212 amino acid (aa) molecule, with a 28 aa signal sequence and a 184 aa mature segment.12-15 It contains four cysteines and two potential N-linked glycosylation sites with its primary structure showing limited homology to G-CSF.15 An alternate splice variant of IL-6 was identified in monocytes and lymphocytes.16 This form is 17 kDa and 148 aa long and appears to lack a binding site for the IL-6 signal transducing molecule gp130. A virally encoded form of IL-6 in human herpesviru