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

M Kopf, H Baumann, G Freer, M Freudenberg… - Nature, 1994 - nature.com
M Kopf, H Baumann, G Freer, M Freudenberg, M Lamers, T Kishimoto, R Zinkernagel…
Nature, 1994nature.com
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 …
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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