The Extension of the Shwartzman Phenomenon to the Mouse and Some Ecological Determinants of the Single-Injection Reaction

Abstract

The localized Shwartzman reaction has been demonstrated in a highly inbred mouse strain (BSVS). This reaction was produced with marked regularity in these mice by administration of relatively small doses of bacterial endotoxin or other Shwartzman-active agents. It is considered the equivalent of the phenomenon described in the rabbit inasmuch as it has conformed to all the operational and histopathological aspects of the classical reaction that have been tested, including elicitation by various endotoxins, heterologous preparation and provocation, inhibition by anticoagulants, and provocation by antigen-antibody complexes. A reaction similar to the above but differing in its manner of production was also investigated and has been termed the single-injection Shwartzman reaction. This phenomenon was identical with the normal Shwartzman reaction in all ways except for the fact that it was elicited with but a single intradermal injection of bacterial endotoxin. In investigating the lesion it has been demonstrated that inapparent in the gross, but elicitible infection of the lungs with a Gram-negative microflora was uniformly associated with single-injection reactivity. Because of this constant association it has been suggested that a causal relationship exists between the infected state and the skin reaction, not on the basis of known immunological events but on the basis of the Shwartzman mechanism in which the lung flora, demonstrably excited by the preparative injection, appears to mediate natural "endogenous" provocation of the lesion at the prepared skin sites.

The Susceptibility of Mice to Bacterial Endotoxins

“…The fact that various colonies of mice differ so consistently in their susceptibility to endotoxins appears at first sight to support the commonly held view that this characteristic is genetically determined (6)(7)(8). Some of our findings, however, point to the role of the bacterial flora in conditioning the response of animals to endotoxins.…”

“…These findings can probably be related to the recent reports of other investigators working with mice and rabbits. Thus, evidence has been presented that mice treated for 2 weeks with terramycin lost the ability to develop hemorrhagic skin lesions (of the Schwartzman type) following a single intradermal injection of endotoxin (7,8). It has been postulated that this loss of reactivity was due to the inhibitory effect of the drug on Gram-negative bacilli in vivo.…”

Endotoxin as Adjuvator to the Transplantation of a Mouse Mammary Tumor

“…Appropriately infected mice not infrequently have enough circulating endotoxin for the evocation of a local Schwartzman reaction by the intradermal injection alone (17). This condition of susceptibility is eliminated by their treatment for 1 month with a suitable antibiotic (17). A high proportion of the mice from the colony kept here give a similar "one-shot" Schwartzman reaction, which is not surprising since they are not rigorously shielded from intestinal bacteria.…”

“…The hemorrhagic necrosis of the skin described by Schwartzman results from intradermal injection of endotoxin followed 24 hr later by intravenous injection of the same substance (16). Appropriately infected mice not infrequently have enough circulating endotoxin for the evocation of a local Schwartzman reaction by the intradermal injection alone (17). This condition of susceptibility is eliminated by their treatment for 1 month with a suitable antibiotic (17).…”