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Impaired immune and acute-phase responses in interleukin-6-deficient mice

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Abstract

lNTERLEUKIN-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune response, acute-phase reaction and haematopoiesis (for reviews see refs 1, 2). In vitro, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and interleukin-11 display overlapping activities with IL-6. This functional redundancy may be explained by the interactions of specific binding receptors with a common signal-transducing receptor (gp130) (for reviews see refs 3, 4). To elucidate the unique function of IL-6 in vivo, we have disrupted the IL-6 gene by homologous recombination. IL-6-deficient mice develop normally. They fail to control efficiently vaccinia virus and infection with Listeria monocytogenes, a facultative intracellular bacterium. The T-cell-dependent antibody response against vesicular stomatitis virus is impaired. Further, the inflammatory acute-phase response after tissue damage or infection is severely compromised, whereas it is only moderately affected after challenge with lipopolysaccharide. We conclude that IL-6 production induced by injury or infection is an important in vivo SOS signal which coordinates activities of liver cells, macrophages and lymphocytes.

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Author notes

  1. Heinz Baumann: To whom correspondence should be addressed

Authors and Affiliations

  1. Max-Planck-lnstitut für Immunbiologie, Stübeweg 51, 79108, Freiburg, Germany

    Manfred Kopf, Marina Freudenberg, Marinus Lamers & Georges Köhler

  2. Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York, 14263, USA

    Manfred Kopf & Georges Köhler

  3. Institut für Experimentelle Immunologie, Universität Zürich, Switzerland

    Giulia Freer & Rolf Zinkernagel

  4. Department of Biology, Hoffmann-La Roche AG, CH-4002, Basel, Switzerland

    Horst Bluethmann

  5. Department of Medicine III, Osaka University, Medical School, Osaka, 565, Japan

    Tadamitsu Kishimoto

Authors
  1. Manfred Kopf
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  2. Heinz Baumann
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  3. Giulia Freer
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  4. Marina Freudenberg
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  5. Marinus Lamers
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  6. Tadamitsu Kishimoto
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  7. Rolf Zinkernagel
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  8. Horst Bluethmann
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  9. Georges Köhler
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Kopf, M., Baumann, H., Freer, G. et al. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368, 339–342 (1994). https://doi.org/10.1038/368339a0

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  • DOI: https://doi.org/10.1038/368339a0

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