IMPAIRED IMMUNE AND ACUTE-PHASE RESPONSES IN INTERLEUKIN-6-DEFICIENT MICE

INTERLEUKIN-6 (IL-6) is a multifunctional cytokine that regulates vari ous aspects of the immune response, acute-phase reaction and haematopo iesis (for reviews see refs 1, 2). In vitro, leukaemia inhibitory fact or, oncostatin M, ciliary neurotrophic factor and interleukin-ll displ ay overlapping activities with IL-6. This functional redundancy may be explained by the interactions of specific binding receptors with a co mmon signal-transducing receptor (gp130) (for reviews see refs 3, 4). To elucidate the unique function of IL-6 in vivo, we have disrupted th e IL-6 gene by homologous recombination. IL-6-deficient mice develop n ormally. They fail to control efficiently vaccinia virus and infection with Listeria mono-cytogenes, a facultative intracellular bacterium. The T-cell-dependent antibody response against vesicular stomatitis vi rus 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 concl ude that IL-6 production induced by injury or infection is an importan t in vivo SOS signal which coordinates activities of liver cells, macr ophages and lymphocytes.