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

Nature. 1994 Mar 24;368(6469):339-42. doi: 10.1038/368339a0.


Interleukin-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.

MeSH terms

  • Acute-Phase Reaction / immunology*
  • Animals
  • B-Lymphocytes / immunology
  • Immunity* / immunology
  • Immunity* / physiology
  • Interleukin-6 / deficiency*
  • Interleukin-6 / genetics
  • Interleukin-6 / physiology
  • Listeriosis / immunology
  • Lymphoid Tissue / embryology
  • Lymphoid Tissue / immunology
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism
  • Rhabdoviridae Infections / immunology
  • T-Lymphocytes / immunology
  • Vesicular stomatitis Indiana virus / immunology


  • Interleukin-6
  • RNA, Messenger