Studies on the Pathogenesis of the Jarisch-Herxheimer Reaction: Development of an Animal Model and Evidence Against a Role for Classical Endotoxin

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Abstract
The etiology of the Jarisch-Herxheimer reaction is unknown, but the reaction may result from toxic products of dead or dying treponemes reacting with sensitized syphilitic tissues. Because of similarities of spirochetes with gram-negative bacteria, endotoxin has been proposed as the responsible toxin. In 19 patients with syphilis, a reaction occurred in 15 (79%) during treatment with penicillin. Endotoxemia was not found by the limulus amoebocyte lysate test. An animal model of the Jarisch-Herxheimer reaction was developed in rabbits infected with Treponema pallidum, When treated with penicillin, 18 (78%) of 23 rabbits infected 18–29 days previously developed a reaction that resembled that in humans. Endotoxernia was not detected by the lysate test. After the reaction, rabbits were not refractory to the pyrogenic effects of endotoxin, and syphilitic rabbits rendered tolerant to endotoxin still developed fever when treated with penicillin. These data suggest that classical endotoxin is not the cause of the Jarisch-Herxheimer reaction.