Production of Generalized Shwartzman Reaction in Rabbits with Nitrogen Mustard-Induced Granulocytopenia. ∗

Abstract

Discussion and Summary

The present results resemble those which Johnstone and Howland(7) obtained with nitrogen mustard and with total body irradiation applied before the local Shwartzman reaction. Their conclusion that there was no threshold granulocyte concentration below which the local Shwartzman reaction cannot be produced was opposed to the earlier findings of Stetson and Good(8) and others(3,9). The situation regarding the generalized Shwartzman reaction has not yet been re-examined.

Thomas and Good in all their experiments gave a preparative dose of endotoxin either 3 days after nitrogen mustard, and none of the 15 rabbits developed the reaction, or they gave nitrogen mustard 12 hours or 6 days prior to endotoxin, and with normal granulocyte counts there was a high incidence of generalized Shwartzman reaction. The experiments, however, show a significant inhibition concomitant with granulocytopenia only 3 days after nitrogen mustard. If the animals were challenged 4 or 5 days after nitrogen mustard with the preparative dose of lipopolysaccharide no inhihitory effect was seen.

It must be concluded from these observations that the inhibitory effect of nitrogen mustard upon the ability of rabbits to react to endotoxins with the peculiar syndrome of generalized Shwartzman reaction. cannot only be due to granulocytopenia. The extent of granulocytopenia 4 and 5 days after nitrogen mustard is the same as on day 3, whereas the incidence of the generalized Shwartzman reaction differs significantly. These findings in part correspond to the unimpaired ability of nitrogen mustard treated leukopenic rabbits to produce an equal fever response to typhoid vaccine as obtained more than a week earlier in the same rabbits(9). In rabbits made granulocytopenic with nitrogen mustard no granulocyte replacement is necessary to make the animals ready to react with the generalized Shwartzman reaction to two appropriately spaced injections of enterobacterial lipopolysaccharide. Only if the preparative dose of lipopolysaccharide was given 3 days after nitrogen mustard is there some inhibition.