Interleukin 6 (IL-6) is a pleiotropic cytokine originally identified in the human as a protein coinduced with interferon-β and as a B-cell stimulatory factor, hence its original names interferon-β2 (Weissenbach et al. 1980), 26-kDa inducible protein (Content et al. 1982) and BSF-2 (Hirano et al. 1985). In the mouse, IL-6 was independently identified as a growth factor for plasmacytomas (Nordan and Potter 1986; Van Snick et al. 1987) and B-cell hybridomas (Van Snick et al. 1986) and was termed plasmacytoma growth factor (PCT-GF) or IL-HP1. Today, it is clear that the biological activity of IL-6 extends far beyond what had been anticipated on the basis of these original findings. Indeed, IL-6 together with IL-1 now appears to be one of the most important macrophage-derived mediators of T-cell activation (Garman et al. 1987; Lotz et al. 1988; Uyttenhove et al. 1988; Houssiau et al. 1988c) and one of the central regulatory proteins involved in the control of acute-phase protein synthesis by the liver (Gauldie et al. 1987). Moreover, it has an important hematopoietic growth factor activity either by itself or in synergy with IL-3 (Ikebuchi et al. 1987; Wong et al. 1988).


Growth Factor Activity Cell Stimulatory Factor Transferrin Receptor Expression Hepatocyte Stimulate Factor 
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  1. Aarden L, Lansdorp P, De Groot E (1985) A growth factor for B cell hybridomas produced by human monocytes. Lymphokines 10:175Google Scholar
  2. Aarden LA (1987) Melchers F, Potter M (eds) Mechanisms of B cell Neoplasia. Roche, Basle, Switzerland, 91–96Google Scholar
  3. Aarden LA, De Groot ER, Schaap OL, Lansdorp PM (1987) Production of hybridoma growth factor by monocytes. Eur J Immunol 17:1411PubMedCrossRefGoogle Scholar
  4. Asaoku H, Kawano M, Iwato K, Tanabe H, Tanaka H, Hirano T, Kishimoto T, Kuramoto A (1988) Decrease in BSF-2/IL-6 response in advanced cases of multiple myeloma. Blood, 72(2): 429–32PubMedGoogle Scholar
  5. Astaldi G, Janssen M, Lansdorp P, Willems C, Zeijlemaker W, Costerhof F (1987) Human endothelial culture supernatant HECS: a growth factor for hybridomas. J Immunol 139:4116Google Scholar
  6. Baroja ML, Ceuppens JL, Van Damme J, Billiau A (1988) Cooperation between an anti-Tcell (anti-CD28) monoclonal antibody monocyte-produced IL-6 in the induction of T cell responsiveness to IL-2. J Immunol 141:1502–1507PubMedGoogle Scholar
  7. Baumann H, Jahreis G, Sauders DN, Koji A (1984) Human keratinocytes and monocytes release factors which regulate the synthesis of major acute phase plasma proteins in hepatic cells from man, rat and mouse. J Biol Chem 259:7331PubMedGoogle Scholar
  8. Brakenhoff JPJ, de Groot ER, Evens R, Pannekoek H, Aarden LA (1987) Molecular cloning and expression of hybridoma growth factor in Eschericia coli. J Immunol 139:4116–4121PubMedGoogle Scholar
  9. Cayphas S, Van Damme J, Vink A, Simpson RJ, Billiau A, Van Snick J (1987) Identification of an interleukin HP1-like plasmacytoma growth factor produced by Lcells in response to viral infection. J Immunol 139:2965PubMedGoogle Scholar
  10. Chen L, Mory Y, Zilberstein A, Revel M (1988) Growth inhibition of human breast carcinoma and leukemia/lymphoma cell lines by recombinant interferon p2. Proc Natl Acad Sci USA 85:8037–8041PubMedCrossRefPubMedCentralGoogle Scholar
  11. Content J, De Wit L, Pierard D, Derynck R, De Clercq E, Fiers W (1982) Secretory proteins induced in human fibroblasts under conditions used for the production of interferon p. Proc Natl Acad Sci USA 79:2768PubMedCrossRefPubMedCentralGoogle Scholar
  12. Content J, De Wit P, Poupart P, Opdenakker G, Van Damme J, Billiau A (1985) Induction of a 26-kDa-protein in RNA in human cells treated with an interleukin-1-related, leukocytederived factor. Eur J Biochem 152:253PubMedCrossRefGoogle Scholar
  13. Coulie PG, Cayphas S, Vink A, Uyttenhove C, Van Snick J (1987) Interleukin-HP1-related hybridoma and plasmacytoma growth factors induced by lipopolysaccharide in vivo. Eur J Immunol 17:1217PubMedCrossRefGoogle Scholar
  14. Coulie PG, Vanhecke A, Van Damme J, Cayphas S, Poupart P, De Wit L, Content J (1987) High-affinity binding sites for human 26-kDa protein (interleukin 6, B cell stimulatory factor- 2, human hybridoma plasmacytoma growth factor, interferon-β2), different from those of type I interferon (alpha, p), on lymphoblastoid cells. Eur J Immunol 17:1435PubMedCrossRefGoogle Scholar
  15. Ferguson-Smith AC, Chen YC, Newman MS, May LT, Sehgal PB, Ruddle FH (1988) Genomics 2:203–208PubMedCrossRefGoogle Scholar
  16. Fiers W, Brouchaert P, Content J, Contreras R, Everaerdt B, Guisez Y, Libert C, Spriggs D, Takahasi N, Tison B, Vandenabeeele P, Van Snick J (1988) Interleukin-6: Biological function and regulation of the gene expression in vitro and in vivo. Proc 4th Congress Immunopharmacol. Osaka, May 16–19Google Scholar
  17. Frei K, Leist T, Meager A, Gallo P, Leppert D, Zindernagel R, Fontana A (1988) Production of B cell stimulatory factor-2 and interferon gamma in the central nervous system during viral meningitis and encephalitis. Evaluation in a murine model infection and in patients. J Exp Med 168:449PubMedCrossRefGoogle Scholar
  18. Garman R, Raulet D (1987) Characterization of a novel murine T cell-activating factor. J Immunol 138:1121PubMedGoogle Scholar
  19. Garman RD, Jacobs KA, Clark SC, Raulet DH (1987) B-cell-stimulatory factor 2 (β2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells. Proc Natl Acad Sci USA 84:7629PubMedCrossRefPubMedCentralGoogle Scholar
  20. Gauldie J, Richards C, Harnish D, Landsdorp P, Baumann H (1987) Interferon-β2/BSF-2 shares identity with monocyte-derived hepatocyte stimulating factor (HSF) and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci USA 84:7251PubMedCrossRefPubMedCentralGoogle Scholar
  21. Geiger T, Andus T, Klapproth J, Hirano T, Kishimoto T, Heinrich P (1988) Induction of rat acute-phase proteins by interleukin-6 in vivo. Eur J Immunol 18(5): 767CrossRefGoogle Scholar
  22. Habu S, Raff M (1977) Accessory cell-dependence of lectin-induced proliferation of mouse T lymphocytes. Eur J Immunol 7:451PubMedCrossRefGoogle Scholar
  23. Haegeman G, Content J, Volckaert G, Derynck R, Tavernier J, Fiers W (1986) Structural analysis of the sequence coding for an inducible 26-kDA protein in human fibroblasts. Eur J Biochem 159:625PubMedCrossRefGoogle Scholar
  24. Helfgott D, May TL, Sthoeger Z, Tamm I, Sehgal PB (1987) Bacterial lipopolysaccharide (endotoxin) enhances expression and secretion of β2 interferon by human fibroblasts. J Exp Med 166:1300PubMedCrossRefGoogle Scholar
  25. Helle M, Brakenhoff J, De Groot E, Aarden L (1988) Interleukin-6 is involved in interleukin- 1-induced activities. Eur J Immunol 18(6): 957PubMedCrossRefGoogle Scholar
  26. Hilbert DM, Cancro MP, Nordan RP, Van Snick J, Rudikoff S (in press) Interleukin 6 is required for a primary immune responseGoogle Scholar
  27. Hilbert DM, Nordan RP, Rudikoff S, submittedGoogle Scholar
  28. Hirano T, Taga T, Nakano N, Yasukawa K, Kashiwamura S, Shimizu K, Nakajima K, Pyun K, Kishimoto T (1985) Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2). Proc Natl Acad Sci USA 82:5490PubMedCrossRefPubMedCentralGoogle Scholar
  29. Hirano T, Teranishi T, Lin B, Onoue K (1984) Human helper T cell factor(s). IV. Demonstration of a human late-acting B cell differentiation factor acting on staphylococcus aureus Cowan I-stimulated B cells. J Immunol 133:798PubMedGoogle Scholar
  30. Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S-I, Nakajima K, Koyama K, Iwamatsu A, Tsunasawa S, Sakyama F, Matsui H, Takahara Y, Taniguchi T, Kishimoto T (1986) Complementary DNA for novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324:73PubMedCrossRefGoogle Scholar
  31. Hodgkin PD, Bond MW, O’Garra A, Frank G, Lee F, Coffman RL, Zlotnik A, Howard M (1988) Identification to IL-6 as a T cell-derived factor that enhances the proliferative response of thymocytes to IL-4 and phorbol myristate acetate. J Immunol 141(1): 151PubMedGoogle Scholar
  32. Horii Y, Muraguchi A, Suematu S, Matsuda T, Yoshizak K, Hirano T, Kishimoto T (1988) Regulation of BSF-2/IL-6 production by human monoclear cells. Macrophage-dependent synthesis of BSF-2/IL-6 by T cells. J Immunol 141:1529PubMedGoogle Scholar
  33. Houssiau F, Coulie PG, Olive D, Van Snick J (1988) Synergistic activation of human cells by interleukin 1 and interleukin 6. Eur J Immunol 18:653PubMedCrossRefGoogle Scholar
  34. Houssiau F, Devogelaer J-P, Van Damme J, Nagant de Deuxchaisnes C, Van Snick J (1988) Interleukin 6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis and Rheumatism 31:784PubMedCrossRefGoogle Scholar
  35. Houssiau FH, Bukasa K, Sindic CJM, Van Damme J, Van Snick (1988) Elevated levels of the 26K human hybridoma growth factor (interleukin 6) in cerebrospinal fluid of patients with acute infection of the central nervous system. Clin Exp Immunol 71:320–323PubMedPubMedCentralGoogle Scholar
  36. Ikebuchi K, Wong GG, Clark SC, Ihle JN, Hirai Y, Ogawa M (1987) Interleukin-6 enhancement of interleukin-3-dependant proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci USA 84:9035PubMedCrossRefPubMedCentralGoogle Scholar
  37. Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H, Kuramoto A, Kishimoto T (1988) Autocrine generation and requirement of BSF- 2/IL-6 for human multiple myelomas. Nature 332:83PubMedCrossRefGoogle Scholar
  38. Larsson EL, Iscove NN, Coutinho A (1980) Two distinct factors are required for induction of T-cell growth. Nature 283:664PubMedCrossRefGoogle Scholar
  39. Lotz M, Jirik F, Kabouridis R, Kabouridis R, Tsoukas C, Hirano T, Kishimoto T, Carson D (1988) B cells stimulating factor 2/interleukin 6 is a constimulant for human thumocytes and T lymphocytes. J Exp Med 167:1253–1258PubMedCrossRefGoogle Scholar
  40. Malek TR, Schmidt JA, Shevach EM (1985) The murine IL 2 receptor. III. Cellular requirement for the induction of IL 2 receptor expression on T cell subpopulations. J Immunol 134:2405PubMedGoogle Scholar
  41. May LY, Helfgott DC, Sehgal PB (1986) Anti-β-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the β2 interferon involved. Proc Natl Acad Sci USA 83:8957PubMedCrossRefPubMedCentralGoogle Scholar
  42. Miyaura C, Onozaki K, Akiyama Y, Taniyama T, Hirano T, Kishimoto T, Suda T (1989) Recombinant human interleukin 6 (B-cell stimulatory factor 2) is a potent inducer of differentiation of mouse myeloid leukemia cells (Ml). Febs Lett 234(1): 17–21CrossRefGoogle Scholar
  43. Mock BA, Nordan RP, Justice JJ, Kozak C, Jenkins NA, Copeland NG, Clark S, Wong G, Rudikoff S (1989) The murine IL-6 gene maps to the proximal region of chromosome 5. J Immunol 142:1372–1376PubMedGoogle Scholar
  44. Muraguchi A, Hirano, Tang B, Matsuda T, Horii Y, Nakajima K, Kishimoto T (1988) The essential role of B cell stimumatory factor 2 (BSF-2/IL6) for the terminal differentiation of B cells. J Exp Med 167:332PubMedCrossRefGoogle Scholar
  45. Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H, Ono M (1986) Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 319:415PubMedCrossRefGoogle Scholar
  46. Neckers LM and Nordan RP (1988) Regulation of murine plasmacytoma transferrin receptor expression and G1 traversal by plasmacytoma cell growth factor. J Cell Physiology 135:495–501CrossRefGoogle Scholar
  47. Neta R, Vogel SN, Sipe JD, Wong GG, Nordan RP (1988) Comparison of in vivo effects of human recombinant IL1 and human recombinant IL6 in mice. Lymphokine Res 7(4): 403PubMedGoogle Scholar
  48. Nijsten M, De Groot E, Ten Duis H, Klasen H, Hack C, Aarden L (1987) Serum levels of interleukin-6 and acute phase responses. The Lancet (II) 921–921CrossRefGoogle Scholar
  49. Nordan R, Potter M (1986) A macrophage-derived factor required by plasmacytomas for survival and proliferation in vitro. Science 233:566PubMedCrossRefGoogle Scholar
  50. Nordan R, Pumphrey J, Rudikoff S (1987) Purification and NH2-terminal amino acid sequence of a plasmacytoma growth factor derived from the murine macrophage cell line. P388D1 J Immunol 139:813Google Scholar
  51. Okada M, Sakaguchi N, Yoshimura N, Hara H, Shimizu K, Yoshida N, Yoshizaki K, Kishimoto S, Yamamura Y, Kishimoto T (1983) B cell growth factors and B cell differentiation factor from human T hybridomas. Two distinct kinds of B cell growth factor and their synergism in B cell proliferation. J Exp Med 157:583PubMedCrossRefGoogle Scholar
  52. Poupart P, Vanderabeele P, Cayphas S, Van Snick J, Haegeman G, Kruys V, Fiers W, Content J (1987) B cell growth modulating and differentiating activity of recombinant human 26-kd protein (BSF-2, HuIFN-β2, HPGF) EMBO J 6:1219PubMedPubMedCentralGoogle Scholar
  53. Reiss LL, Le J, Hirano T, Kishimoto T, Vilcek J (1988) Antiviral action of tumor necrosis factor in human fibroblasts is not mediated by B cell stimulatory factor 2/IFN-P2, and is inhibited by specific antibodies to IFN-β. J Immunol 140:1566Google Scholar
  54. Revel M, Chen L, Mory Y, Zilberstein A, Michalevicz R (1988) Interferon-type and other activities of IFN-β-2/BSF-2/HSF. Proceedings of the 4th Congress of Immunopharmacology May 1988, OsakaGoogle Scholar
  55. Satoh T, Nakamura S, Taga T, Matsuda T, Hirano T, Kishimoto T, Kaziro Y (1988) Induction of neuronal differentiation in PC 12 cells by B-cell stimulatory factor 2/interleukin 6. Mol Cell Biol 8(8):3546–49PubMedPubMedCentralGoogle Scholar
  56. Seghal PB, Walther Z, Tamm I (1987) Rapid enhancement of B2-IFN/BSF-2 gene expression in human fibroblasts by diacylglycerols and the calcium ionophore A23187. Proc Natl Acad Sci USA 84:3633CrossRefGoogle Scholar
  57. Seghal PB, Sagar AD (1980) Heterogeneity of poly(I). poly (c)-induced human fibroblast interferon mRNA species. Nature 288:95CrossRefGoogle Scholar
  58. Seghal PB, Zilberstein A, Ruggieri RM, May LT, Ferguson-Smith A, Late DL, Revel M, Ruddle FM (1987) Human chromosome 7 carries the β2 interferon gene. Proc Natl Acad Sci USA 84:3633CrossRefGoogle Scholar
  59. Simpson RJ, Moritz RL, Rubira MR, Van Snick J (1988) Murine hybridoma/plasmacytoma growth factor: complete amino acid sequence and relation to human interleukin-6. Eur J Biochem 176:187–197PubMedCrossRefGoogle Scholar
  60. Smith KA, Lachman LB, Oppenheim JJ, Favata M (1980) The functional relationship of the interleukins. J Exp Med 151:1551PubMedCrossRefGoogle Scholar
  61. Staerz UD, Bevan MJ (1986) Activation of resting T lymphocytes by a monoclonal antibody directed against an allotypic determinant on the T cell receptor. Eur J Immunol 16:263PubMedCrossRefGoogle Scholar
  62. Taga T, Kawanishi Y, Hardy R, Hirano T, Kishimoto T (1987) Receptors for B cell stimulatory factor 2. Quantitation, specificity, distribution and regulation of their expression. J Exp Med 166:967PubMedCrossRefGoogle Scholar
  63. Takai Y, Wong G, Clark S, Burakoff S, Herrmann S (1988) B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes. J Immunol 140:508PubMedGoogle Scholar
  64. Tanabe O, Akira S, Kamiya T, Wong G, Hirano T, Kishimoto T (1988) Genomic structure of the murine IL-6 gene. High degree of conservation of potential regulatory sequences between mouse and human. J Immunol 141:3875PubMedGoogle Scholar
  65. Tosato G, Seamon KB, Goldman ND, Sehgal PB, May LT, Washington GC, Jones KD, Pike SE (1988) Monocyte-derived human B-cell growth factor identified as interferon-β2 (BSF-2, IL6), Science 239:502PubMedCrossRefGoogle Scholar
  66. Tsuchiya M, Asano S, Kaziro Y, Nagata S (1986) Isolation and characterization of the cDNA for murine granulocyte colony-stimulating factor. Proc Natl Acad Sci USA 83:7633PubMedCrossRefPubMedCentralGoogle Scholar
  67. Uyttenhove C, Coulie PG, Van Snick JT (1988) T cell growth and differentiation induced by interleukin-HPl/IL6, the murine hybridoma/plasmacytoma growth factor. J Exp Med 167:1417PubMedCrossRefGoogle Scholar
  68. Van Damme J, Cayphas S, Opdenakker G, Billiau A, Van Snick J (1987) Interleukin 1 and poly(rl).poly(rC) induce production of a hybridoma growth factor by human fibroblasts. Eur J Immunol 17:1PubMedCrossRefGoogle Scholar
  69. Van Damme J, Opdenakker G, Simpson RJ, Rubira MR, Cayphas S, Vink A, Billiau A, Van Snick J (1987) Identification of the human 26-kD protein, interferon β2 (IFN-β2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 2 and tumor necrosis factor. J Exp Med 165:914PubMedCrossRefGoogle Scholar
  70. Van Damme J, Van Beeumen J, Decock B, Van Snick J, De Ley M, Billiau F (1988) Separation and comparison of two monokines with LAF activity (interleukin-1β and hybridoma growth factor): identification of leukocyte-derived HGF as interleukin-6. J Immunol 140:1534PubMedGoogle Scholar
  71. Van Snick J, Cayphas S, Szikora J-P, Renauld J-C, Van Roost E, Boon T, Simpson RJ (1988) cDNA cloning of murine interleukin-HP1: homology with human interleukin 6. Eur J Immunol 18:193PubMedCrossRefGoogle Scholar
  72. Van Snick J, Cayphas S, Vink A, Uyttenhove C, Coulie P, Simpson T (1986) Purification and NH2-terminal amino acid sequence of a new T cell-derived lymphokine with growth factor activity for B cell hybridomas. Proc Natl Acad Sci USA 83:9679PubMedCrossRefPubMedCentralGoogle Scholar
  73. Van Snick J, Cayphas S, Vink A, Uyttenhove C, Coulie P, Simpson R (1986) Purification and NH2-terminal amino acid sequence of a new T cell-derived lymphokine with growth factor activity for B cell hybridomas. Proc Natl Acad Sci USA 83:9679PubMedCrossRefPubMedCentralGoogle Scholar
  74. Van Snick J, Vink A, Cayphas S, Uyttenhove C (1987) Interleukin HP1, a T cell-derived hybridoma growth factor that supports the in vitro growth of murine plasmacytomas. J Exp Med 165:641PubMedCrossRefGoogle Scholar
  75. Vink A, Coulie PG, Wauters P, Nordan RP, Van Snick J (1986) B cell growth and differentiation activity of interleukin-HP1 and related murine plasmacytoma growth factors. Synergy with interleukin 1. Eur J Immunol 18:607CrossRefGoogle Scholar
  76. Weissenbach J, Chernajovsky Y, Zeevi M, Shulman L, Sorecq H, Nir U, Wallach D, Perricaudet M, Tiollais P, Revel M (1980) Two interferon mRNAs in human fibroblasts: in vitro translation and Escherichia Coli cloning studies. Proc Natl Acad Sci USA 77:7152PubMedCrossRefPubMedCentralGoogle Scholar
  77. Wong GG, Clark SC (1988) Multiple actions of interleukin 6 within a cytokine network. Immunol Today 9:137PubMedCrossRefGoogle Scholar
  78. Wong GG, Witek-Giannotti J, Temple P, Kriz R, Ferenz C, Hewick R, Clark SC, Ikebuchi K, Ogawa M (1988) Stimulation of murine homopoietic colony formation by human IL-6. J Immunol 140:3040PubMedGoogle Scholar
  79. Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, Taniguchi T, Hirano T, Kishimoto T (1988) Cloning and expression of the human interleukin-6 (BSF-2/IFN β2) receptor. Science 241:825PubMedCrossRefGoogle Scholar
  80. Yasukawa K, Hirano T, Watanabe Y, Muratani K, Matsuda T, Kishimoto T (1987) Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene. EMBO. J 6:2939PubMedPubMedCentralGoogle Scholar
  81. Zhang Y, Lin JX, Vilcek J (1988) Synthesis of interleukin 6 (interferon-β2/B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP. J Biol Chem 263(13):6177PubMedGoogle Scholar
  82. Zilberstein A, Ruggieri R, Korn JH, Revel M (1986) Structure and expression of cDNA and genes for human interferon-β2, a distinct species inducible by growth-stimulatory cytokines. Embo J 5:2529PubMedPubMedCentralGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • J. Van Snick
  • R. P. Nordan

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