Impaired immune and acute-phase responses in interleukin-6-deficient mice.
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.
Kopf
M
M
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Baumann
H
H
Freer
G
G
Freudenberg
M
M
Lamers
M
M
Kishimoto
T
T
Zinkernagel
R
R
Bluethmann
H
H
Köhler
G
G
D000210:Acute-Phase Reaction / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D007109:Immunity / Q000276:immunology / Q000502:physiology; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D008088:Listeriosis / Q000276:immunology; D008221:Lymphoid Tissue / Q000196:embryology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D018353:Rhabdoviridae Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D015850:Interleukin-6; D012333:RNA, Messenger