Murine IL-12 is involved in Calmette-Guérin bacillus-induced sensitization and is by itself sufficient to sensitize mice to the lethal effects of human TNF1.
Human TNF, a specific agonist of murine (m)TNF-R55, is fairly harmless in healthy mice, but readily induces lethality in animals sensitized by a malignant tumor or a bacterial infection. We here report that IL-12 is both a necessary and sufficient mediator in Calmette-Guérin bacillus-induced sensitization to the lethal effects of hTNF. Evidence for this involvement is provided by the protection observed after anti-mIL-12 Ab treatment and by the fact that Calmette-Guérin bacillus-induced sensitization can be mimicked by repetitive mIL-12 administration. IL-12 exerts this effect by inducing IFN-gamma in NK cells. Tumor-induced sensitization, however, does not seem to involve mIL-12.
Cauwels
A
A
Laboratory of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and Ghent University, Ghent, Belgium.
Fiers
W
W
Brouckaert
P
P
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology*; D017471:Receptors, Interferon / Q000502:physiology; D014376:Tuberculosis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D000096743:Interferon gamma Receptor
D015703:Antigens, CD; D007371:Interferon-gamma; D018664:Interleukin-12; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor