Studies on T H E Generalized Shwartzman Reaction* Ii. the Production of Bilateral Cortical Necrosis 0]~ the Kidneys by a Single Injection of Bacterial Toxin in Rabbits Previously Treated with Thorotrast or Trypan Blue

In an earlier communication (1), it was shown that treatment with cortisone caused a marked alteration in the response of rabbits to an injection of endotoxin from certain Gram-negative microorganishas. In normal animals, an intradermal injection of meningococcal or Serratia marcescens toxin resulted in a vigorous local inflammatory reaction, with visible erythema and edema of the involved skin. In cortisone-treated rabbits, there was little evidence of local inflammation; instead, numerous small hemorrhages appeared throughout the injected skin area. Histologically, these skin lesions showed occlusion of the small vessels by masses of leukocytes and platelets, an event shown by Stetson (2) to be characteristic of the developing Shwartzman reaction. Similarly, a single intravenous injection of toxin, which caused no tissue lesions in normal rabbits, was found to produce bilateral cortical necrosis of the kidneys in cortisone-treated animals. The renal lesion was identical with that of the generalized Shwartzman reaction, which is produced by giving two intravenous injections of toxin spaced 12 to 24 hours apart. These observations indicated that cortisone had an effect which was equivalent to one phase of the Shwartzman reaction. In attempting to account for the effect, the possibility was considered that a mechanism responsible for the removal, detoxification, or fixation of toxin might be interfered with by cortisone. Indirect evidence for such interference was obtained in the following manner. In normal rabbits very large amounts of meningococcal toxin can be injected intradermally without causing systemic intoxication and without pro-