Interleukin-6 in Biology and Medicine

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This chapter focuses on structure and expression of interleukin-6 (IL-6), which is a cytokine with pleiotropic activities that plays a central role in host defense. IL-6 can exert growth-inducing, growth-inhibitory, and differentiation-inducing activities, depending on the target cells. These activities include (1) terminal differentiation (secretion of immunoglobulins) in B cells and (2) growth promotion on various B cells. IL-6 has been implicated in the pathology of many diseases including multiple myeloma, mesangial proliferative glomerulonephritis, rheumatoid arthritis, and acquired immunodeficiency syndrome (AIDS). Selective inhibition of the synthesis or of the action of IL-6 may have therapeutic benefit against the IL-6-associated diseases. On the other hand, IL-6 has potent antitumor activity against certain types of tumors. Application of IL-6 is promising in cancer treatment as well as in treatment of radiation- or chemotherapy-induced myelosuppression. The cell biology of the intracellular events that link transduction to gene regulation is an important area, and work on these topics helps to understand such phenomena as multifunction of IL-6 and bidirectional effects of cell growth depending on the cell type.

References (429)

  • BroideD.H. et al.

    Cytokines in symptomatic asthma airways

    J. Allergy Clin. Immunol.

    (1992)
  • BursteinS.A. et al.

    Thrombocytosis in normal and sublethally irradiated dogs: Response to human interleukin 6

    Blood

    (1992)
  • CalderonT.M. et al.

    Interleukin 6 modulates c-sis gene expression in cultured human endothelial cells

    Cell. Immunol.

    (1992)
  • CrowlR.M. et al.

    Induction of phospholipase A2 gene expression in human hepatoma cells by mediators of the acute phase response

    J. Biol. Chem.

    (1991)
  • DickJ.E. et al.

    Gene transfer into normal human hematopoietic cells using in vitro and in vivo assays

    Blood

    (1991)
  • DuttonR.W. et al.

    Is there evidence for a nonantigen specific diffusable chemical mediator from the thymus cell in the initiation of the immune response?

    Prog. Immunol.

    (1971)
  • Ferguson-SmithA.C. et al.

    Regional localization of the interferon-β-cell stimulatory factor 2/hepatocyte stimulating factor gene to human chromosome 7pl5-21

    Genomics

    (1988)
  • FlemingI. et al.

    Incubation with endotoxin activates the L-arginine pathway in vascular tissue

    Biochem. Biophys. Res. Commun.

    (1990)
  • GalloP. et al.

    Human immunodeficiency virus type I(HIV-1) infection of the central nervous system: An evaluation of cytokines in the cerebrospinal fluid

    J. Neuroimmunol.

    (1989)
  • GanterU. et al.

    α2-Macroglobulin synthesis in interleukin-6-stimulated human neuronal(SH-SY5Y neuroblastoma) cells, Potential significance for the processing of Alzheimer β-amyloid precursor protein

    FEBS Lett.

    (1991)
  • GeisslerK. et al.

    In vivo synergism of recombinant human interleukin-3 and recombinant human interleukin-6 on thrombopoiesis in primates

    Blood

    (1992)
  • GivonT. et al.

    Antitumor effects of human recombinant interleukin-6 on acute myeloid leukemia in mice and in cell cultures

    Blood

    (1992)
  • AardenL.A. et al.

    A growth factor for B cell hybridomas produced by human monocytes

    Lymphokines

    (1985)
  • AardenL.A. et al.

    Production of hybridoma growth factor by human monocytes

    Eur. J. Immunol.

    (1987)
  • AbramowiczD. et al.

    Release of tumor necrosis factor, interleukin-2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients

    Transplantation

    (1989)
  • AderkaD. et al.

    IL-6 inhibits liposaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice

    J. Immunol.

    (1989)
  • AkiraS. et al.

    Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF)

    FASEBJ.

    (1990)
  • AkiraS. et al.

    A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family

    EMBO J.

    (1990)
  • AkiraS. et al.

    IL-6 and NF-IL6 in acute-phase response and viral infection

    Immunol. Rev.

    (1992)
  • AmadoriA. et al.

    HIV-specific B cell activation: A major constituent of spontaneous B cell activation during HIV-infection

    J. Immunol.

    (1989)
  • AmbrosinoD.M. et al.

    Human polysaccharide-specific B cells are responsive to pokeweed mitogen and IL-6

    J. Immunol.

    (1990)
  • AstaldiG.C.B. et al.

    Human endothelial culture supernatant (HECS): A growth factor for hybridomas

    J. Immunol.

    (1980)
  • BatailleR. et al.

    IL-6 is a potent growth factor for plasma cells and is elevated in overt myeloma and plasma cell leukemia

    J. Clin. Invest.

    (1989)
  • BatailleR. et al.

    The critical role of interleukin-6, interleukin-1β and macrophage colony-stimulating factor in the pathogenesis of bone lesions in multiple myeloma

    Int. J. Clin. Lab. Res.

    (1992)
  • BauerJ. et al.

    Regulation of interleukin 6 receptor expression in human monocytes and monocyte-derived macrophages

    J. Exp. Med.

    (1989)
  • BauerJ. et al.

    Interleukin-6 in clinical medicine

    Ann Hematol.

    (1991)
  • BaumannH. et al.

    Interleukin-11 regulates the hepatic expression of the same plasma protein genes as interleukin-6

    J. Biol. Chem.

    (1992)
  • BaumannH. et al.

    Hepatocyte-stimulating factor III shares structural and functional indentity with leukemia-inhibitory factor

    J. Immunol.

    (1989)
  • BazanJ.F.

    Structural design and molecular evolution of a cytokine receptor superfamily

    Proc. Natl. Acad. Sci. U.S.A.

    (1990)
  • BeagleyK.W. et al.

    Interleukins and IgA synthesis: Human and murine interleukin 6 induce high rate IgA secretion in IgA-committed B cells

    J. Exp. Med.

    (1989)
  • BeckerS. et al.

    Cytokine (tumor necrosis factor, IL-6, and IL-8) production by respiratory syncytial virus-infected human alveolar macrophages

    J. Immunol.

    (1991)
  • BendtzenK. et al.

    Possible role of IL-1, TNF-α, and IL-6 in insulin-dependent diabetes mellitus and autoimmune thyroid disease

    Lymphokine Res.

    (1989)
  • BhardwajN. et al.

    IL-6/IFN-β2 in synovial effusions of patients with rheumatoid arthritis and other arthritides

    J. Immunol.

    (1989)
  • BlackK. et al.

    Chinese hamster ovarian cells transfected with the murine interleukin-6 gene cause hypercalcemia as well as cachexia, leukocytosis and thrombocytosis in tumor-bearing nude mice

    Endocrinology

    (1991)
  • BlankensteinT. et al.

    DNA rearrangement and constitutive expression of the interleukin 6 gene in a mouse plasmacytoma

    J. Exp. Med.

    (1990)
  • BlayJ.-Y. et al.

    Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma

    Cancer Res.

    (1992)
  • BloemenaE. et al.

    Kinetics of interleukin 6 during OKT3 treatment in renal allograft recipients

    Transplantation

    (1990)
  • BodineD.M. et al.

    Combination of interleukin 3 and 6 preserves stem cell function in culture and enhances retrovirus-mediated gene transfer into hematopoietic stem cells

    Proc. Natl. Acad. Sci. U.S.A.

    (1989)
  • BrakenhoffJ.P. et al.

    Molecular cloning and expression of hybridoma growth factor in

    Escherichia coli. J. Immunol.

    (1987)
  • BrakenhoffJ.P. et al.

    Analysis of human IL-6 mutants expressed in Escherichia coli: Biologic activities are not affected by deletion of amino acids 1-28

    J. Immunol.

    (1989)
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