Response of interleukin-6-deficient mice to tumor necrosis factor-induced metabolic changes and lethality.
Whether interleukin (IL)-6 contributes to tumor necrosis factor (TNF)-induced lethal shock or whether, on the contrary, it is part of a protective feedback system, remains unresolved. Here, we report experiments with IL-6 gene-disrupted mice (IL-6(0/0)). We have tested the susceptibility of these to TNF-induced metabolic changes and lethality in different models, and compared the results with those obtained with IL-6+/+ wild-type mice. We studied the response to TNF in three different models: (i) murine TNF administration; (ii) TNF in galactosamine (GalN)-sensitized mice; (iii) TNF in Bacillus Calmette-Guérin-sensitized mice. We observed no significant difference between the two types of mice in any of the three models. Furthermore, IL-6(0/0) mice could be equally well desensitized (by IL-1) to TNF/GalN-induced lethality and tolerized to TNF-induced shock as IL-6+/+ mice. We also observed that, in response to turpentine, TNF or IL-1, IL-6(0/0) mice produced significantly less acute phase proteins (APP) than IL-6+/+ mice. In IL-6(0/0) mice, less corticosterone was induced by TNF than in the control mice, while the response to adrenocorticotropic hormone was the same. The results indicate that IL-6 is not contributing in a major way to the pathogenesis leading to TNF-induced shock, and that neither IL-6 nor the APP studied are essential for a protective feedback system.
Libert
C
C
Laboratory of Molecular Biology, University, Gent, Belgium.
Takahashi
N
N
Cauwels
A
A
Brouckaert
P
P
Bluethmann
H
H
Fiers
W
W
D000209:Acute-Phase Proteins / Q000096:biosynthesis; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D003345:Corticosterone / Q000096:biosynthesis; D005688:Galactosamine / Q000633:toxicity; D007108:Immune Tolerance; D015850:Interleukin-6 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D014425:Turpentine / Q000633:toxicity
D000209:Acute-Phase Proteins; D001500:BCG Vaccine; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D003345:Corticosterone; D014425:Turpentine