Abstract
Cytokines are protein mediators of cell-to-cell communication important in a variety of physiologic and pathophysiologic processes. Only a decade ago information about cytokines was limited to the description of a multitude of ill-defined “factors” present in crude super- natants of cultures of mononuclear cells. Modern techniques of protein chemistry and molecular biology have led to the isolation and precise functional definition of many cytokines, including the interferons, colony-stimulating factors, and a heterogeneous group of agents termed interleukins. The name “interleukins” was originally conceived to designate proteins produced by lymphocytes or monocytes, affecting the growth and/or differentiation of lymphoid, monocytic or myeloid cells. With time it has become apparent that many interleukins are not produced exclusively by white blood cells, nor are their actions restricted to leukocytes. The terms “interleukin” or “lymphokine” are now being used for cytokines that can be produced by a variety of cell types and that can affect the functions of many nonhematopoietic cells.
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References
Aarden LA, Lansdorp PM, DeGroot ER: A growth factor for B cell hybridomas produced by human monocytes. Lymphokines 10:175, 1985
Aarden LA, DeGroot ER, Schaap OL, Lansdorp PM: Production of hybridoma growth factor by human monocytes. Eur J Immunol 17:1411, 1987
Aderka D, Le J, Vilček J: Interleukin-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells and in mice. J Immunol, in press 1989
Andus T, Geiger T, Hirano T, Northoff H, Ganter U, Bauer J, Kishimoto T, Heinrich PC: Recombinant human B cell stimulatory factor 2 (BSF-2/IFN-beta2) regulates beta-fibrinogen and albumin mRNA levels in Fao-9 cells. FEBS Lett 221:18, 1987
Astaldi GCB, Janssen MC, Lansdorp P, Willems C, Zeijlemaker WP, Oosterhof F: Human endothelial culture supernatant (HECS): a growth factor for hybridomas. J Immunol 125:1411, 1980
Baroja ML, Ceuppens JL, Van Damme J, Billiau A: Cooperation between an anti-T cell (anti-CD28) monoclonal antibody and monocyte-produced IL-6 in the induction of T cell responsiveness to IL-2. J Immunol 141:1502, 1988
Baumann H, Onorato V, Gauldie J, Jahreis GP: Distinct sets of acute phase plasma proteins are stimulated by separate human hepatocyte-stimulating factors and monokines in rat hepatoma cells. J Biol Chem 262:9756, 1987
Baumann H, Richards C, Gauldie J: Interaction among hepatocyte-stimulating factors, interleukin 1, and glucocorticoids for regulation of acute phase plasma proteins in human hepatoma (Hep G2) cells. J Immunol 139:4122, 1987
Baumann H, Won K-A, Jahreis GP: Human hepatocyte-stimulating factor-III and interleukin-6 are structurally and immunologically distinct but regulate the production of the same acute phase plasma proteins. J Biol Chem 264:8046, 1989
Bazin R, Lemieux R: role of the macrophage-derived hybridoma growth factor in the in vitro and in viuo proliferation of newly formed B cell hybridomas. J Immunol 139:780, 1987
Beagley KW, Eldridge JH, Lee F, Kiyono H, Everson MP, Koopman WJ, Hirano T, Kishimoto T, McGhee JR: Interleukins and IgA synthesis. Human and murine interleukin 6 induce high rate IgA secretion in IgA-committed B cells. J Exp Med 169:2133, 1989
Billiau A: BSF-2 is not just a differentiation factor. Nature (London) 324:415, 1986
Billiau A: Interferon-beta2 as a promoter of growth and differentiation of B cells. Immunol Today 8:84, 1987
Biondi A, Rossi V, Bassan R, Barbui T, Bettoni S, Sironi M, Mantovani A, Rambaldi A: Constitutive expression of the interleukin-6 gene in chronic lymphocytic leukemia. Blood 73:1279, 1989
Bot FJ, Van Eijk L, Broeders L, Aarden LA, Löwenberg B: Interleukin-6 synergizes with M-CSF in the formation of macrophage colonies from purified human marrow progenitor cells. Blood 73:435, 1989
Bowcock AM, Kidd JR, Lathrop M, Daneshvar L, May LT, Ray A, Sehgal PB, Kidd KK, Cavalli-Sforza LL: The human “ft interferon/hepatocyte stimulating factor/interleukin-6” gene: DNA polymorphism studies and localization to chromosome 7p21. Genomics 3:8, 1988
Brakenhoff JPJ, DeGroot ER, Evers RF, Pannekoek H, Aarden LA: Molecular cloning and expression of hybridoma growth factor in Escherichia coli. J Immunol 139:4116, 1987
Brakenhoff JPJ, Hart M, Aarden LA: Analysis of human IL-6 mutants expressed in Escherichia coli. Biologic activities are not affected by deletion of amino acids 1-28. J Immunol 143:1175, 1989
Brouckaert P, Spriggs DR, Demetri G, Kufe DW, Fiers W: Circulating interleukin 6 during a continuous infusion of tumor necrosis factor and interferon 7. J Exp Med 169:2257, 1989
Cayphas S, Van Damme J, Vink A, Simpson RJ, Billiau A, Van Snick J: Identification of an interleukin HP1-like plasmacytoma growth factor produced by L cells in response to viral infection. J Immunol 139:2965, 1987
Ceuppens JL, Baroja ML, Lorre K, Van Damme J, Billiau A: Human T cell activation with phytohemagglutinin. The function of IL-6 as an accessory signal. J Immunol 141:3868, 1988
Chen L, Mory Y, Zilberstein A, Revel M: Growth inhibition of human breast carcinoma and leukemia/lymphoma cell lines by recombinant interferon-beta2. Proc Natl Acad Sci USA 85:8037, 1988
Chiu C-P, Moulds C, Coffman RL, Rennick D, Lee F: Multiple biological activities are expressed by a mouse interleukin 6 cDNA clone isolated from bone marrow stromal cells. Proc Natl Acad Sci USA 85:7099, 1988
Chiu C-P, Lee F: IL-6 is a differentiation factor for Ml and WEHI-3B myeloid leukemic cells. J Immunol 142:1909, 1989
Collins T, Lapierre LA, Fiers W, Strominger JL, Pober JS: Recombinant human tumor necrosis factor increases mRNA levels and surface expression of HLA-A,B antigens in vascular endothelial cells and dermal fibroblasts in vitro. Proc Natl Acad Sci USA 83:446, 1986
Content J, De Wit L, Pierard D, Derynck R, De Clercq E, Fiers W: Secretory proteins induced in human fibroblasts under conditions used for the production of interferon beta. Proc Natl Acad Sci USA 79:2768, 1982
Content J, De Wit L, Poupart P, Opdenakker G, Van Damme J, Billiau A: Induction of a 26-kDa-protein mRNA in human cells treated with an interleukin-1-related, leukocyte-derived factor. Eur J Biochem 152:253, 1985
Corbel C, Melchers F: The synergism of accessory cells and of soluble alpha-factors derived from them in the activation of B cells to proliferation. Immunol Rev 78:51, 1984
Coulie PG, Cayphas S, Vink A, Uyttenhove C, Van Snick J: Interleukin-HP1-related hybridoma and plasmacytoma growth factors induced by lipopolysaccharide in vivo. Eur J Immunol 17:1217, 1987
Coulie PG, Vanhecke A, Van Damme J, Cayphas S, Poupart P, De Wit L, Content J: High-affinity binding sites for human 26-kDa protein (interleukin 6, B cell stimulatory factor-2, human hybridoma plasmacytoma growth factor, interferon-beta2), different from those of type I interferon (alpha, beta), on lymphoblastoid cells. Eur J Immunol 17:1435, 1987
Darlington GJ, Wilson DR, Lachman LB: Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hepatoma cells in vitro. J Cell Biol 103:787, 1986
Defilippi P, Poupart P, Tavernier J, Fiers W, Content J: Induction and regulation of mRNA encoding 26-kI)a protein in human cell lines treated with recombinant human tumor necrosis factor. Proc Natl Acad Sci USA 84:4557, 1987
De Maeyer E, De Maeyer-Guignard J: Interferons and Other Regulatory Cytokines. New York, John Wiley and Sons, 1988
Derynck R, Content J, DeClercq E, Volckaert G, Tavernier J, Devos R, Fiers W: Isolation and structure of a human fibroblast interferon gene. Nature (London) 285:542, 1980
Elias J, Trinchieri G, Beck JM, Simon PL, Sehgal PB, May LT, Kern JA: A synergistic interaction of IL-6 and IL-1 mediates the thymocyte-stimulating activity produced by recombinant IL-1-stimulated fibroblasts. J Immunol 142:509, 1989
Ferguson-Smith AC, Chen Y-F, Newman MS, May LT, Sehgal PB, Ruddle FH: Regional localization of the beta2-interferon/B-cell stimulatory factor 2/hepatocyte stimulating factor gene to human chromosome 7p15-p21 Genomics 2:203, 1988
Fong Y, Moldawer LL, Marano M, Wei H, Tatter SB, Clarick RH, Santhanam U, Sherris D, May LT, Sehgal PB, Lowry SF: Endotoxemia elicits increased circulating β2-IFN/IL-6 in man. J Immunol 142:2321, 1989
Frei K, Leist TP, Meager A, Gallo P, Leppert D, Zinkernagel RM, Fontana A: 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 168:449, 1988
Frei K, Malipiero UV, Leist TP, Zinkernagel RM, Schwab ME, Fontana A: On the cellular source and function of interleukin 6 produced in the central nervous system in viral diseases. Eur J Immunol 19:689, 1989
Carman RD, Jacobs KA, Clark SC, Raulet DH: B-cell-stimulatory factor 2 (beta2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells. Proc Natl Acad Sci USA 84:7629, 1987
Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H: Interferon beta2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci USA 84:7251, 1987
Geiger T, Andus T, Klapproth J, Hirano T, Kishimoto T, Heinrich PC: Induction of rat acute-phase proteins by interleukin 6 in vivo. Eur J Immunol 18:717, 1988
Grossman RM, Krueger J, Yourish D, Granelli-Piperno A, Murphy DP, May LT, Kupper TS, Sehgal PB, Gottlieb AB: Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes. Proc Natl Acad Sci USA 86:6367, 1989
Gurney ME, Apatoff BR, Spear GT, Baumel MJ, Antel JP, Bania MB, Reder AT: Neuroleukin: a lymphokine product of lectin-stimulated T cells. Science 234:574, 1986
Haegeman G, Content J, Volckaert G, Derynck R, Tavernier J, Fiers W: Structural analysis of the sequence coding for an inducible 26-kDa protein in human fibroblasts. Eur J Biochem 159:625, 1986
Helfgott DC, May LT, Sthoeger Z, Tamm I, Sehgal PB: Bacterial lipopolysaccharide (endotoxin) enhances expression and secretion of beta2 interferon by human fibroblasts. J Exp Med 166:1300, 1987
Helfgott DC, Tatter SB, Santhanam U, Clarick RH, Bhardwaj N, May LT, Sehgal PB: Multiple forms of IFN-β2/IL-6 in serum and body fluids during acute bacterial infection. J Immunol 142:948, 1989
Helle M, Brakenhoff JPJ, DeGroot ER, Aarden LA: Interleukin 6 is involved in interleukin 1-induced activities. Eur J Immunol 18:957, 1988
Helle M, Boeije L, Aarden LA: IL-6 is an intermediate in IL-1-induced thymocyte proliferation. J Immunol 142:4335, 1989
Hirano T, Teranishi T, Lin B, Onoue K: 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 133:798, 1984
Hirano T, Taga T, Nakano N, Yasukawa K, Kashiwamura S, Shimizu K, Nakajima K, Pyun KH, Kishimoto T: Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2). Proc Natl Acad Sci USA 82:5490, 1985
Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Koyama K, Iwamatsu A, Tsunasawa S, Sakiyama F, Matsui H, Takahara Y, Taniguchi T, Kishimoto T: Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature (London) 324:73, 1986
Hirano T, Taga T, Yasukawa K, Nakajima K, Nakano N, Tak-atsuki F, Shimizu M, Murashima A, Tsunasawa S, Sakiyama F, Kishimoto T: Human B-cell differentiation factor defined by an anti-peptide antibody and its possible role in autoantibody production. Proc Natl Acad Sci USA 84:228, 1987
Hirano T, Matsuda T, Hosoi K, Okano A, Matsui H, Kishimoto T: Absence of antiviral activity in recombinant B cell stimulatory factor 2 (BSF-2). Immunol Lett 17:41, 1988
Hirano T, Matsuda T, Turner M, Miyasaka N, Buchan G, Tang B, Sato K, Shimizu M, Maini R, Feldmann M, Kishimoto T: Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol 18:1797, 1988
Hirano T, Kishimoto T: Interleukin-6. In Handbook of Experimental Pharmacology, Peptide Growth Factors and Their Receptors, edited by Sporn MB, Roberts AB, Berlin, Springer-Verlag, in press 1990
Hodgkin PD, Bond MW, O’Garra A, Frank G, Lee F, Coffman RL, Zlotnik A, Howard M: Identification of IL-6 as a T cell-derived factor that enhances the proliferative response of thymocytes to IL-4 and phorbol myristate acetate. J Immunol 141:151, 1988
Horii Y, Muraguchi A, Suematsu S, Matsuda T, Yoshizaki K, Hirano T, Kishimoto T: Regulation of BSF-2/IL-6 production by human mononuclear cells. Macrophage-dependent synthesis of BSF-2/IL-6 by T cells. J Immunol 141:1529, 1988
Houssiau FA, Bukasa K, Sindic CJM, Van Damme J, Van Snick J: 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, 1988
Houssiau FA, Coulie PG, Olive D, Van Snick J: Synergistic activation of human T cells by interleukin 1 and interleukin 6. Eur J Immunol 18:653, 1988
Ikebuchi K, Wong GG, Clark SC, Ihle JN, Hirai Y, Ogawa M: Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci USA 84:9035, 1987
Ishibashi T, Kimura H, Uchida T, Kariyone S, Friese P, Burstein SA: Human interleukin 6 is a direct promoter of maturation of megakaryocytes in vitro. Proc Natl Acad Sci USA 86:5953, 1989
Jablons DM, Mule JJ, McIntosh JK, Sehgal PB, May LT, Huang CM, Rosenberg SA, Lotze MT: IL-6/IFN-β2 as a circulating hormone. Induction by cytokine administration in humans. J Immunol 142:1542, 1989
Jambou RC, Snouwaert JN, Bishop GA, Stebbins JR, Frelinger JA, Fowlkes DM: High-level expression of a bioengineered, cysteine-free hepatocyte-stimulating factor (interleukin 6)-like protein. Proc Natl Acad Sci USA 85:9426, 1988
Jirik FR, Podor TJ, Hirano T, Kishimoto T, Loskutoff DJ, Carson DA, Lotz M: Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J Immunol 142:144, 1989
Kasid A, Director EP, Rosenberg SA: Induction of endogenous cytokine-mRNA in circulating peripheral blood mononuclear cells by IL-2 administration to cancer patients. J Immunol 143:736, 1989
Katz Y, Strunk RC: IL-1 and tumor necrosis factor similarities and differences in stimulation of expression of alternative pathway of complement and IFN-β2/IL-6 genes in human fibroblasts. J Immunol 142:3862, 1989
Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H, Kuramoto A, Kishimoto T: Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature (London) 332:83, 1988
Kawano M, Tanaka H, Ishikawa H, Nobuyoshi M, Iwato K, Asaoku H, Tanabe O, Kuramoto A: Interleukin-1 accelerates autocrine growth of myeloma cells through interleukin-6 in human myeloma. Blood 73:2145, 1989
Kelker HC, Le J, Rubin BY, Yip YK, Nagler C, Vilček J: Three molecular weight forms of natural human interferon-gamma revealed by immunoprecipitation with monoclonal antibody. J Biol Chem 259:4301, 1984
Kirnbauer R, Köck A, Schwarz T, Urbanski A, Krutmann J, Borth W, Damm D, Shipley G, Ansel JC, Luger TA: IFN-β2, B cell differentiation factor 2, or hybridoma growth factor (IL-6) is expressed and released by human epidermal cells and epidermoid carcinoma cell lines. J Immunol 142:1922, 1989
Kishimoto T, Hirano T: Molecular regulation of B lymphocyte response. Ann Rev Immunol 6:485, 1988
Kishimoto T, Taga T, Yamazaki K, Kawanishi K, Hirata Y, Yahata H, Hirano T: High and low affinity receptors for BSF-2/ IL-6 and their organization (abstr 8912). FASEB J 2:A1830, 1988
Klein B, Zhang X-G, Jourdan M, Content J, Houssiau F, Aarden L, Piechaczyk M, Bataille R: Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6. Blood 73:517, 1989
Kohase M, Henriksen-DeStefano D, May LT, Vilček J, Sehgal PB: Induction of beta2-interferon by tumor necrosis factor: a homeostatic mechanism in the control of cell proliferation. Cell 45:659, 1986
Kohase M, May LT, Tamm I, Vilček J, Sehgal PB: A cytokine network in human diploid fibroblasts: interactions of beta-interferons, tumor necrosis factor, platelet-derived growth factor, and interleukin-1. Mol Cell Biol 7:273, 1987
Kohase M, Zhang Y, Lin J-X, Yamazaki S, Sehgal PB, Vilček J: Interleukin-1 can inhibit interferon-beta synthesis and its antiviral action: comparison with tumor necrosis factor. J Interferon Res 8:559, 1988
Koike K, Nakahata T, Takagi M, Kobayashi T, Ishiguro A, Tsuji K, Naganuma K, Okano A, Akiyama Y, Akabane T: Synergism of BSF-2/interleukin 6 and interleukin 3 on development of multipotential hemopoietic progenitors in serum-free culture. J Exp Med 168:879, 1988
Koj A: Definition and classification of acute-phase proteins. In The Acute-Phase Response to Injury and Infection, edited by Gordon AH, Koj A, p 139, Amsterdam, Oxford, and New York, Elsevier, 1985
Koj A, Gauldie J, Sweeney GD, Regoeczi E, Sauder DN: A simple bioassay for monocyte-derived hepatocyte stimulating factor: increased synthesis of alpha 2-macroglobulin and reduced synthesis of albumin by cultured rat hepatocytes. J Immunol Methods 76:317, 1985
Kunimoto DY, Nordan RP, Strober W: IL-6 is a potent cofactor of IL-1 in IgM synthesis and of IL-5 in IgA synthesis. J Immunol 143:2230, 1989
Le J, Vilček J: Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest 56:234, 1987
Le J, Fredrickson G, Reis LFL, Diamantstein T, Hirano T, Kishimoto T, Vilček J: Interleukin 2-dependent and interleukin 2-independent pathways of regulation of thymocyte function by interleukin 6. Proc Natl Acad Sci USA 85:8643, 1988
Le J, Reis LFL, Vilček J: Tumor necrosis factor and interleukin 1 can act as essential growth factors in a murine plasmacytoma line. Lymphokine Res 7:99, 1988
Le J, Fredrickson G, Pollack M, Vilček J: Activation of thymocytes and T cells by interleukin 6. Ann NY Acad Sci 557:444, 1989
Leary AG, Ikebuchi K, Hirai Y, Wong GG, Yang YC, Clark SC, Ogawa M: Synergism between interleukin-6 and interleukin-3 in supporting proliferation of human hematopoietic stem cells: comparison with interleukin-1 alpha. Blood 71:1759, 1988
Leeuwenberg JFM, Van Damme J, Jeunhomme GMAA, Buurman WA: Interferon-beta1, an intermediate in the tumor necrosis factor alpha-induced increased MHC class I expression and an autocrine regulator of the constitutive MHC class I expression. J Exp Med 166:1180, 1987
Lew W, Oppenheim JJ, Matsushima K: Analysis of the suppression of IL-1α and IL-1β production in human peripheral blood mononuclear adherent cells by a glucocorticoid hormone. J Immunol 140:1895, 1988
Lotz M, Jirik F, Kabouridis P, Tsoukas C, Hirano T, Kishimoto T, Carson DA: B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med 167:1253, 1988
Lotz M, Vaughan JH, Carson DA: Effect of neuropeptides on production of inflammatory cytokines by human monocytes. Science 241:1218, 1988
Luger TA, Krutmann J, Kirnbauer R, Urbanski A, Schwarz T, Klappacher G, Köck A, Micksche M, Malejczyk J, Schauer E, May LT, Sehgal PB: IFN-β2/IL-6 augments the activity of human natural killer cells. J Immunol 143:1206, 1989
Marinkovic S, Jahreis GP, Wong GG, Baumann H: IL-6 modulates the synthesis of a specific set of acute phase plasma proteins in vivo. J Immunol 142:808, 1989
Matsuda T, Hirano T, Kishimoto T: Establishment of an interleukin 6 (IL-6)/B cell stimulatory factor 2-dependent cell line and preparation of anti-IL-6 monoclonal antibodies. Eur J Immunol 18:951, 1988
Matsuda T, Hirano T, Nagasawa S, Kishimoto T: Identification of α2-macroglobulin as a carrier protein for IL-6. J Immunol 142:148, 1989
May LT, Helfgott DC, Sehgal PB: Anti-beta-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the beta2 interferon involved. Proc Natl Acad Sci USA 83:8957, 1986
May LT, Ghrayeb J, Santhanam U, Tatter SB, Sthoeger Z, Helfgott DC, Chiorazzi N, Grieninger G, Sehgal PB: Synthesis and secretion of multiple forms of beta2-interferon/B-cell differentiation factor 2/hepatocyte stimulating factor by human fibroblasts and monocytes. J Biol Chem 263:7760, 1988
May LT, Santhanam U, Tatter SB, Bhardwaj N, Ghrayeb J, Sehgal PB: Phosphorylation of secreted forms of human beta2-interferon/hepatocyte stimulating factor/interleukin-6. Biochem Biophys Res Commun 152:1144, 1988
McIntosh JK, Jablons DM, Mule JJ, Nordan RP, Rudikoff S, Lotze MT, Rosenberg SA: In vivo induction of IL-6 by administration of exogenous cytokines and detection of de novo serum levels of IL-6 in tumor-bearing mice. J Immunol 143:162, 1989
McKenzie D: Alloantigen presentation by B cells. Requirement for IL-1 and IL-6. J Immunol 141:2907, 1988
Miyaura C, Onozaki K, Akiyama Y, Taniyama T, Hirano T, Kishimoro T, Suda T: Recombinant human interleukin 6 (B-cell stimulatory factor 2) is a potent inducer of differentiation of mouse myeloid leukemia cells (Ml). FEBS Lett 234:17, 1988
Mock BA, Nordan RP, Justice MJ, Kozak C, Jenkins NA, Copeland NG, Clark SC, Wong GG, Rudikoff S: The murine IL-6 gene maps to the proximal region of chromosome 5. J Immunol 142:1372, 1989
Morrone G, Ciliberto G, Oliviero S, Arcone R, Dente L, Content J, Cortese R: Recombinant interleukin 6 regulates the transcriptional activation of a set of human acute phase genes. J Biol Chem 263:12554, 1988
Muraguchi A, Kishimoto T, Miki Y, Kuritani T, Kaieda T, Yoshizaki K, Yamamura Y: T cell-replacing factor (TRF)-induced IgG secretion in a human B blastoid cell line and demonstration of acceptors for TRF. J Immunol 127:412, 1981
Muraguchi A, Hirano T, Tang B, Matsuda T, Horii Y, Nakajima K, Kishimoto T: The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med 167:332, 1988
Nakajima K, Martinez-Maza O, Hirano T, Breen EC, Nishanian PG, Salazar-Gonzalez JF, Fahey JL, Kishimoto T: Induction of IL-6 (B cell stimulatory factor-2/IFN-β2) production by HIV. J Immunol 142:531, 1989
Namba Y, Hanaoka M: Immunocytology of cultured IgM-forming cells of mouse. I Requirement of phagocytic cell factor for the growth of IgM-forming tumor cells in tissue culture. J Immunol 109:1193, 1972
Navarro S, Debili N, Bernaudin J-F, Vainchenker W, Doly J: Regulation of the expression of IL-6 in human monocytes. J Immunol 142:4339, 1989
Neta R, Vogel SN, Sipe JD, Wong GG, Nordan RP; Comparison of in vivo effects of human recombinant IL-1 and human recombinant IL-6 in mice. Lymphokine Res 7:403, 1988
Nijsten MWN, DeGroot ER, Ten Duis HJ, Klasen HJ, Hack CE, Aarden LA: Serum levels of interleukin-6 and acute phase responses. Lancet ii:921, 1987
Nishimoto N, Yoshizaki K, Tagoh H, Monden M, Kishimoto S, Hirano T, Kishimoto T: Elevation of serum interleukin 6 prior to acute phase proteins on the inflammation by surgical operation. Clin Immunol Immunopathol 50:399, 1989
Noma T, Mizuta T, Rosen A, Hirano T, Kishimoto T, Honjo T: Enhancement of the interleukin 2 receptor expression on T cells by multiple B-lymphotropic lymphokines. Immunol Lett 15:249, 1987
Nordan RP, Potter M: A macrophage-derived factor required by plasmacytomas for survival and proliferation in vitro. Science 233:566, 1986
Nordan RP, Pumphrey JG, Rudikoff S: Purification and NH2-terminal sequence of a plasmacytoma growth factor derived from the murine macrophage cell line P388D1. J Immunol 139:813, 1987
Okada M, Sakaguchi N, Yoshimura N, Hara H, Shimizu K, Yoshida N, Yoshizaki K, Kishimoto S, Yamamura Y, Kishimoto T: 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 157:583, 1983
Okada M, Kitahara M, Kishimoto S, Matsuda T, Hirano T, Kishimoto T: IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol 141:1543, 1988
Onozaki K, Akiyama Y, Okano A, Hirano T., Kishimoto T, Hashimoto T, Yoshizawa K, Taniyama T: Synergistic regulatory effects of interleukin 6 and interleukin 1 on the growth and differentiation of human and mouse myeloid leukemic cell lines. Cancer Res 49:3602, 1989
Paul WE, Laughlin CA, Johnston MI: Report of nomenclature discussion. Ann NY Acad Sci 557:579, 1989
Perlmutter DH, Dinarello CA, Punsal PI, Colten HR: Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest 78:1349, 1986
Pober JS: The multiple roles of tumor necrosis factor. Ann Inst Pasteur/Immunol 139:337, 1988
Poupart P, Vandenabeele P, Cayphas S, Van Snick J, Haegeman G, Kruys V, Fiers W, Content J: B cell growth modulating and differentiating activity of recombinant human 26-Kd protein (BSF-2, HuIFN-beta2, HPFG). EMBO J 6:1219, 1987
Ramadori G, Sipe JD, Dinarello CA, Mizel SB, Colten HR: Pretranslational modulation of acute phase hepatic protein synthesis by murine recombinant interleukin 1 (IL-1) and purified human IL-1. J Exp Med 162:930, 1985
Ramadori G, Van Damme J, Rieder H, Meyer zum Büschenfelde K-H: Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1β and tumor necrosis factor-α. Eur J Immunol 18:1259, 1988
Ray A, Tatter SB, May LT, Sehgal PB: Activation of the human “beta2-interferon/hepatocyte-stimulating factor/interleukin 6” promoter by cytokines, viruses, and second messenger agonists. Proc Natl Acad Sci USA 85:6701, 1988
Reis LFL, Le J, Hirano T, Kishimoto T, Vilček J: Antiviral action of tumor necrosis factor in human fibroblasts is not mediated by B cell stimulatory factor 2/IFN-beta2, and is inhibited by specific antibodies to IFN-beta. J Immunol 140:1566, 1988
Reis LFL, Lee TH, Vilček J: Tumor necrosis factor acts synergistically with autocrine interferon-β and increases interferon-β mRNA levels in human fibroblasts. J Biol Chem, 264:1635, 1989
Rennick D, Jackson J, Yang G, Wideman J, Lee F, Hudak S: Interleukin-6 interacts with interleukin-4 and other hematopoietic growth factors to selectively enhance the growth of megakaryocytic, erhthroid, myeloid, and multipotential progenitor cells. Blood 73:1828, 1989
Revel M: Genetic and functional diversity of interferons in man. In Interferon 1983, Vol 5, edited by Gresser I, p 205. London, Academic Press, 1983
Revel M, Zilberstein A, Ruggieri R, Chen L, Mory Y, Rubinstein M, Michalevicz R: Human interferon beta2: a multifunctional cytokine. In Tumor Necrosis Factor/Cachectin and Related Cytokines, edited by Bonavida B, Gifford GE, Kirchner H, Old LJ, p 252. Karger, 1988
Ritchie DG, Fuller GM: Hepatocyte stimulating factor: a monocyte-derived acute-phase regulatory protein. Ann NY Acad Sci 408:490, 1983
Sachs L, Lotem J, Shabo Y: The molecular regulators of macrophage and granulocyte development. Role of MGI-2/IL-6. Ann NY Acad Sci 557:417, 1989
Sagar AD, Sehgal PB, Slate DS, Ruddle FH: Multiple human beta interferon genes. J Exp Med 156:744, 1982
Saiki O, Ralph P: Clonal differences in response to T cell replacing factor (TRF) for IgM secretion and TRF receptors in a human B lymphoblast cell line. Eur J Immunol 13:31, 1983
Sato T, Matsui H, Shibahara S, Kobayashi T, Morinaga Y, Kashima N, Yamasaki S, Hamuro J, Taniguchi T: New approaches for the high-level expression of human interleukin-2 cDNA in Escherichia coli. J Biochem 101:525, 1987
Satoh T, Nakamura S, Taga T, Matsuda T, Hirano T, Kishimoto T, Kaziro Y: Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6. Mol Cell Biol 8:3546, 1988
Sehgal PB: The interferon genes. Biochim Biophys Acta 695:17, 1982
Sehgal PB, Sagar AD: Heterogeneity of poly(I)poly(C)-induced human fibroblast interferon mRNA species. Nature (London) 288:95, 1980
Sehgal PB, May LT: Human interferon-beta2. J Interferon Res 7:521, 1987
Sehgal PB, Zilberstein A, Ruggieri M-R, May LT, Ferguson-Smith A, Slate DL, Revel M, Ruddle FH: Human chromosome 7 carries the beta2 interferon gene. Proc Natl Acad Sci USA 83:5219, 1986
Sehgal PB, May LT, Tamm I, Vilček J: Human beta2 interferon and B-cell differentiation factor BSF-2 are identical. Science 235:731, 1987
Sehgal PB, Walther Z, Tamm I: Rapid enhancement of beta2-interferon/B-cell differentiation factor BSF-2 gene expression in human fibroblasts by diacylglycerols and the calcium ionophore A23187. Proc Natl Acad Sci USA 84:3663, 1987
Sehgal PB, Helfgott DC, Santhanam U, Tatter SB, Ciarick RH, Ghrayeb J, May LT: Regulation of the acute phase and immune responses in viral disease. Enhanced expression of the beta2 — interferon/hepatocyte-stimulating factor/interleukin 6 gene in virus-infected human fibroblasts. J Exp Med 167:1951, 1988
Sehgal PB, Greininger G, Tosato G (Editors): Regulation of the Acute Phase and Immune Responses: Interleukin-6. Ann NY Acad Sci V. 557:1–583, 1989
Shabo Y, Lotem J, Rubinstein M, Revel M, Clark SC, Wolf SF, Kamen R, Sachs L: The myeloid blood cell differentiation-inducing protein MGI-2A is interleukin 6. Blood 72:2070, 1988
Shenkin A, Fraser WD, Series J, Winstanley FP, McCartney AC, Burns HJG, Van Damme J: The serum interleukin 6 response to elective surgery. Lymphokine Res 8:123, 1989
Shimizu K, Hirano T, Ishibashi K, Nakano N, Taga T, Sugamura K, Yamamura Y, Kishimoto T: Immortalization of BGDF (BCGF II)-and BCDF-producing T cells by human T cell leukemia virus (HTLV) and characterization of human BGDF (BCGF II). J Immunol 134:1728, 1985
Shimizu S, Yoshioka R, Hirose Y, Sugai S, Tachibana J, Konda S: Establishment of two interleukin 6 (B cell stimulatory factor 2/interferonβ2)-dependent human bone marrow-derived myeloma cell lines. J Exp Med 169:339, 1989
Shrestha K, Hiramoto RN, Ghanta VK: Regulation of MOPC 104E by T cells and growth factors induced by ```C parvum`` stimulation. Int J Cancer 33:845, 1984
Siegall CB, Chaudhary VK, FitzGerald DJ, Pastan I: Cytotoxic activity of an interleukin 6-Pseudomonas exotoxin fusion protein on human myeloma cells. Proc Natl Acad Sci USA 85:9738, 1988
Sims JE, March CJ, Cosman D, Widmer MB, MacDonald HR, McMahan CJ, Grubin CE, Wignall JM, Jackson JL, Call SM, Friend D, Alpert AR, Gillis S, Urdal DL, Dower SK; cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily. Science 241:585, 1988
Sironi M, Breviario F, Proserpio P, Biondi A, Vecchi A, Van Damme J, Dejana E, Mantovani A: IL-1 stimulates IL-6 production in endothelial cells. J Immunol 142:549, 1989
Suematsu S, Matsuda T, Aozasa K, Akira S, Nakano N, Ohno S, Miyazaki J-I, Yamamura K-I, Hirano T, Kishimoto T: IgGl plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci USA 86:7547, 1989
Sugasawara RJ, Cahoon BE, Karu AE: The influence of murine macrophage-conditioned medium on cloning efficiency, antibody synthesis and growth rate of hybridomas. J Immunol Methods 79:263, 1985
Sutton MGJ, Mercier L, Giuliani E, Lie JT: Atrial myxomas. A review of clinical experience in 40 patients. Mayo Clin Proc 55:371, 1980
Tabibzadeh SS, Santhanam U, Sehgal PB, May LT: Cytokineinduced production of IFN-β/IL-6 by freshly explanted human endometrial stromal cells. Modulation by estradiol-17β. J Immunol vn142:3134, 1989
Taga T, Kawanishi Y, Hardy RR, Hirano T, Kishimoto T: Receptors for B cell stimulatory factor 2. Quantitation, specificity, distribution, and regulation of their expression. J Exp Med 166:967, 1987
Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hiaron T, Kishimoto T: Interleukin-6 triggers the association of its receptor with a possible signal transducer, gpl30. Cell 58:573, 1989
Takai Y, Wong GG, Clark SC, Burakoff SJ, Herrmann SH: B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes. J Immunol 140:508, 1988
Takatsuki F, Okano A, Suzuki C, Chieda R, Takahara Y, Hirano T, Kishimoto T, Hamuro J, Akiyama Y: Human recombinant IL-6/B-cell stimulatory factor 2 augments murine antigen-specific antibody responses in vitro and in vivo. J Immunol 141:3072, 1988
Tanabe O, Akira S, Kamiya T, Wong GG, Hirano T, Kishimoto T: Genomic structure of the murine IL-6 gene. High degree conservation of potential regulatory sequences between mouse and human. J Immunol 141:3875, 1988
Teranishi T, Hirano T, Arima N, Onoue K: Human helper T cell factor(s) (ThF) II. Induction of IgG production in B lymphoblastoid cell lines and identification of T cell-replacing factor (TRF)-like factors. J Immunol 128:1903, 1982
Tosato G, Pike SE: Interferon-beta2/interleukin 6 is a co-stimulant for human T lymphocytes. J Immunol 141:1556, 1988
Tosato G, Seamon KB, Goldman ND, Sehgal PB, May LT, Washington GC, Jones KD, Pike SE: Monocyte-derived human B-cell growth factor identified as interferon-beta, (BSF-2, IL-6). Science 239:502, 1988
Tovey MG, Content J, Gresser I, Gugenheim J, Blanchard B, Guymarho J, Poupart P, Gigou M, Shaw A, Fiers W: Genes for IFN-β2 (IL-6), tumor necrosis factor, and IL-1 are expressed at high levels in the organs of normal individuals. J Immunol 141:3106, 1988
Ulich TR, del Castillo J, Guo K: In vivo hematologie effects of recombinant interleukin-6 on hematopoiesis and circulating numbers of RBCs and WBCs. Blood 73:108, 1989
Uyttenhove C, Coulie PG, Van Snick J: T cell growth and differentiation induced by interleukin-HP1/IL-6, the murine hybridoma/plasmacytoma growth factor. J Exp Med 167:1417, 1988
Van Damme J, Cayphas S, Opdenakker G, Billiau A, Van Snick J: Interleukin 1 and poly(rI)poly(rC) induce production of a hybridoma growth factor by human fibroblasts. Eur J Immunol 17:1, 1987
Van Damme J, De Ley M, Van Snick J, Dinarello CA, Billiau A: The role of interferon-beta1 and the 26-kDa protein (interferon-beta2) as mediators of the antiviral effect of interleukin 1 and tumor necrosis factor. J Immunol 139:1867, 1987
Van Damme J, Opdenakker G, Simpson RJ, Rubira MR, Cayphas S, Vink A, Billiau A, Van Snick J: Identification of the human 26-kD protein, interferon beta2 (IFN-beta2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor. J Exp Med 165:914, 1987
Van Damme J, Schaafsma MR, Fibbe WE, Falkenburg JHF, Opdenakker G, Billiau A: Simultaneous production of interleukin 6, interferon-β and colony-stimulating activity by fibroblasts after viral and bacterial infection. Eur J Immunol 19:163, 1989
Van der Meer JWM, Helle M, Aarden L: Comparison of the effects of recombinant interleukin 6 and recombinant interleukin 1 on nonspecific resistance to infection. Eur J Immunol 19:413, 1989
Van Oers MHJ, Van der Heyden AAPAM, Aarden LA: Interleukin 6 (IL-6) in serum and urine of renal transplant recipients. Clin Exp Immunol 71:314, 1988
Van Snick J, Cayphas S, Vink A, Uyttenhove C, Coulie PG, Rubira MR, Simpson RJ: Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. Proc Natl Acad Sci USA 83:9679, 1986
Van Snick J, Vink A, Cayphas S, Uyttenhove C: Interleukin-HP1, a T cell-derived hybridoma growth factor that supports the in vitro growth of murine plasmacytomas. J Exp Med 165:641, 1987
Van Snick J, Cayphas S, Szikora J, Renauld J, Van Roost E, Boon T, Simpson RJ: cDNA cloning of murine interleukin-HP1: homology with human interleukin 6. Eur J Immunol 18:193, 1988
Vankelecom H, Carmeliet P, Van Damme J, Billiau A, Denef C: Production of interleukin-6 by folliculo-stellate cells of the anterior pituitary gland in a histiotypic cell aggregate culture system. Neuroendocrinology 49:102, 1989
Vercelli D, Jabara HH, Arai K-I, Yokota T, Geha RS: Endogenous interleukin 6 plays an obligatory role in interleukin 4-dependent human IgE synthesis. Eur J Immunol 19:1419, 1989
Vilček J: Interferons. In Handbook of Experimental Pharmacology, Peptide Growth Factors and Their Receptors, edited by Sporn MB, Roberts AB, Berlin, Springer-Verlag, in press 1990
Vilček J, Palombella VJ, Zhang Y, Lin J-X, Feinman R, Reis LFL, Le J: Mechanisms and significance of the mitogenic and antiviral actions of TNF. Ann Inst Pasteur/Immunol 139:281, 1988
Vink A, Coulie PG, Wauters P, Nordan RP, Van Snick J: B cell growth and differentiation activity of interleukin-HPl and related murine plasmacytoma growth factors. Synergy with interleukin 1. Eur J Immunol 18:607, 1988
Waage A, Brandtzaeg P, Halstensen A, Kierulf P, Espevik T: The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome. J Exp Med 169:333, 1989
Waage A, Kaufmann C, Espevik T, Husby G: Interleukin-6 in synovial fluid from patients with arthritis. Clin Immunol Immunopathol 50:394, 1989
Walker KZ, Gibson J, Axiak SM, Prentice RL: Potentiation of hybridoma production by the use of mouse fibroblast conditioned media. J Immunol Methods 88:75, 1986.
Walther Z, May LT, Sehgal PB: Transcriptional regulation of the interferon-beta2/B cell differentiation factor BSF-2/hepatocyte-stimulating factor gene in human fibroblasts by other cytokines. J Immunol 140:974, 1988
Weissenbach J, Chernajovsky Y, Zeevi M, Shulman L, Soreq H, Nir U, Wallach D, Perricaudet M, Tiollais P, Revel M: Two interferon mRNAs in human fibroblasts: In vitro translation and Escherichia coli cloning studies. Proc Natl Acad Sci USA 77:7152, 1980
Weissmann C, Weber H: The interferon genes. In Progr Nucl Acid Res Mol Biol edited by Cohn WE, Moldave K, 33:251, Orlando, Academic Press, 1986
Woloski BMRNJ, Fuller GM: Identification and partial characterization of hepatocyte-stimulating factor from leukemia cell lines: comparison with interleukin 1. Proc Natl Acad Sci USA 82:1443, 1985
Woloski BMRNJ, Smith EM, Meyer WJ III, Fuller GM, Blalock JE: Corticotropin-releasing activity of monokines. Science 230:1035, 1985
Wong GG, Clark SC: Multiple actions of interleukin 6 within a cytokine network. Immunol Today 9:137, 1988
Wong GG, Witek-Giannotti JS, Temple PA, Kriz R, Ferenz C, Hewick RM, Clark SC, Ikebuchi K, Ogawa M: Stimulation of murine hemopoietic colony formation by human IL-6. J Immunol 140:3040, 1988
Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, Taniguchi T, Hirano T, Kishimoto T: Cloning and expression of the human interleukin-6 (BSF-2/IFN-beta2) receptor. Science 241:825, 1988
Yasukawa K, Hirano T, Watanabe Y, Muratani K, Matsuda T, Nakai S, Kishimoto T: Structure and expression of human B cell stimulatory factor-2 (BSF-2/1L-6) gene. EMBO J 6:2939, 1987
Zhang Y, Lin J-X, Vilček J: Synthesis of interleukin 6 (interferon-beta2/B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP. J Biol Chem 263:6177, 1988
Zhang Y, Lin J-X, Yip YK, Vilček J: Enhancement of cAMP levels and of protein kinase activity by tumor necrosis factor and interleukin 1 in human fibroblasts: role in the induction of interleukin 6. Proc Natl Acad Sci USA 85:6802, 1988
Zilberstein A, Ruggieri R, Korn JH, Revel M: Structure and expression of cDNA and genes for human interferon-beta2, a distinct species inducible by growth-stimulatory cytokines. EMBO J 5:2529, 1986
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Le, J., Vilček, J. (1990). Interleukin 6: A Multifunctional Cytokine Regulating Immune Reactions and the Acute Phase Protein Response. In: Rubin, E., Damjanov, I. (eds) Pathology Reviews • 1990. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-0485-5_7
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