Immunomodulatory cytokine produced by a wide variety of mammalian cell types including macrophages, monocytes, T cells, B cells and keratinocytes. Inhibits the synthesis of proinflammatory cytokines such as interleukin-1 and tumor necrosis factor α. Upregulates humoral immune responses and attenuates cell-mediated immune reactions. Protein composed of 160 amino acid residues; mol wt 18.5 kDa. Exists as a homodimer; the native human form has little or no glycosylation. A viral analog has been identified that is produced by Epstein Barr virus (EBV). Discovery: D. F. Fiorentino et al., J. Exp. Med. 170, 2081 (1989). Cloning and expression of murine form and homology with product of EBV gene BCRFI: K. W. Moore et al., Science 248, 1230 (1990). Review of discovery, properties and biological function: T. R. Mosmann, Adv. Immunol. 56, 1-26 (1994). Review of potential clinical applications in inflammatory disease: I. Lalani et al., Ann. Allergy Asthma Immunol. 79, 469-483 (1997); in infectious diseases: S. M. Opal et al., Clin. Infect. Dis. 27, 1497-1507 (1998); in inflammatory bowel disease: M. W. Leach et al., Toxicol. Pathol. 27, 123-133 (1999). Review: K. Asadullah et al., Pharmacol. Rev. 55, 241-269 (2003).
Human form produced in E. coli by recombinant DNA technology. Production: T. R. Mosmann et al., EP 405980; eidem, US 5231012 (1991, 1993 both to Schering). Clinical pharmacokinetics: E. Radwanski et al., Pharm. Res. 15, 1895 (1998). Clinical effect on circulating leukocyte populations: R. D. Huhn et al., Immunopharmacology 41, 109 (1999).