The
Shwartzman reaction is elicited by two
injections of
lipopolysaccharide (LPS) in mice. The priming LPS injection is given in the footpad, whereas the lethal LPS challenge is given intravenously 24 h later. The injection of
interferon gamma (IFN-gamma) or
interleukin 12 (IL-12) instead of the LPS priming injection induced the lethal reaction in mice further challenged with LPS.
Antibodies against IFN-gamma when given together with the priming agent, prevented the lethal reaction in mice primed with either LPS,
IL-12, or IFN-gamma.
Antibodies against
IL-12, when given together with the priming agent, prevented the lethal reaction in mice primed with either LPS or
IL-12 but not with IFN-gamma. These results strongly suggest that LPS induces the release of
IL-12, that
IL-12 induces the production of IFN-gamma, and that IFN-gamma is the
cytokine that primes macrophages and other cell types. Upon LPS challenge, the lethal
Shwartzman reaction is induced by a massive production of inflammatory
cytokines that act on the target sites already sensitized by IFN-gamma. If mixtures of TNF and
IL-1 or mixtures of TNF and IFN-gamma are used to challenge mice previously primed with IFN-gamma or
IL-12, mortality is induced. In the same conditions, the individual
cytokines or a mixture of
IL-1 and IFN-gamma do not replace the LPS challenge. When the mice are primed with LPS, the combination of TNF,
IL-1, and IFN-gamma induced only a partial mortality incidence suggesting that the involvement of other LPS-induced factors.