THE ROLE OF ENDOTOXIN DURING TYPHOID FEVER AND TULAREMIA IN MAN. I. ACQUISITION OF TOLERANCE TO ENDOTOXIN*

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Abstract
Employing each human subject as his own control, it was found that a high degree of tolerance to the pyrogenic action of Salmonella typhosa and Escherichia coii endotoxins is acquired by afebrile days 3 to 12 following convalescence from induced typhoid fever. Such tolerance was not attributable to the residual effects of control testing with endotoxin, nor to the chloramphenicol employed for therapy. Significant tolerance to S. typhosa endotoxin developed by afebrile convalescent days 3 to 8 following human tularemia induced by either the intradermal or aerosol route. No significant tolerance to endotoxin developed in subjects given viable S. typhosa or Pasteurella tularensis who failed to manifest overt illness, or those given a viral disease, sandfly fever. Such findings support the premise that physiologically active quantities of circulating endotoxin contribute to the pathogenesis of typhoid fever and tularemia in man.