Certain factors involved in the production of the generalized
Shwartzman reaction with meningococcal toxin in rabbits were investigated. The optimal amounts of toxin for the preparing and provoking
injections, and the optimal time interval between
injections were determined. Under suitable conditions of dosage and timing, bilateral cortical
necrosis of the kidneys was produced in a high proportion of animals. When excessive amounts of toxin were used for preparation the incidence of the reaction was reduced. Animals undergoing the generalized
Shwartzman reaction became severely prostrated within several hours after the provoking injection of toxin. The renal lesion became fully developed within 24 hours, and its occurrence was associated with a rise of the blood non-
protein nitrogen.
Edema and petechial
hemorrhages in the ears were observed in rabbits with advanced renal lesions. The earliest change in the kidneys in the generalized
Shwartzman reaction was the appearance of homogeneous, eosinophilic material, resembling fibrinoid, within the lumen of the glomerular capillaries. Occlusion of the capillaries by this material was regarded as the cause of subsequent tubular
necrosis in the renal cortex. The material appeared to be derived from the blood, rather than from the capillary walls.
Cortisone enhanced the lethal effect of a single, large dose of meningococcal toxin, as well as causing bilateral
renal cortical necrosis. The generalized
Shwartzman reaction produced by two
injections of toxin was aggravated by
cortisone and
ACTH. Profound polymorphonuclear
leukopenia was produced by both the preparing and provoking
injections of toxin. When
leukopenia was produced before the preparing injection of toxin, by treatment with
nitrogen mustard, the generalized
Shwartzman reaction was inhibited. During the intervals before and after
leukopenia, and when
leukopenia was prevented by shielding the femoral bone marrow from the action of
nitrogen mustard, no inhibition of the generalized
Shwartzman phenomenon was demonstrable. Various colloidal and particulate materials, which are capable of provoking the local skin
Shwartzman reaction when injected intravenously, failed to provoke the generalized
Shwartzman reaction. A working hypothesis was set up to account for certain events in the generalized
Shwartzman reaction.