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The Journal of Immunology, Vol 156, Issue 12 4686-4690, Copyright © 1996 by American Association of Immunologists

ARTICLES

Murine IL-12 is involved in Calmette-Guerin bacillus-induced sensitization and is by itself sufficient to sensitize mice to the lethal effects of human TNF1

A Cauwels, W Fiers and P Brouckaert
Laboratory of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and Ghent University, Ghent, Belgium.

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-Guerin 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-Guerin 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.


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