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Although the presence of endotoxin has been suspected in the circulating blood of patients suffering from Gram-negative infections, it was not possible until recently to produce evidence to support this contention.The unusual sensitivity of the rabbit skin to endotoxin in the presence of epinephrine (accelerated Shwartzman reaction) led us to use this reaction as a test for circulating endotoxin (1). As described by Thomas (2), a striking hemorrhagic necrosis develops at the intracutaneous site of epinephrine injection, if the animal has received an intravenous injection of endotoxin during the preceding 4 hours. When pla~na from infected patients is utilized for the intravenous injection, positive results are reliably obtained in patients with protracted hypotension or shock. When attempts were made to estimate the quantity of endotoxin present by injecting known amounts of endotoxin in a vehicle of normal human plasma, and in saline, it was found that human plasma mixed with endotoxin not only enhances the local reactivity of the rabbit to intracutaneous injections of epinephrine, but also potentiates the lethal effect of endotoxin administered intravenously by approximately 10,000-fold.Plasma has been reported both to potentiate, and to inhibit the effects of endotoxin.Farr (3) found a tenfold enhancement of pyrogenic and leucocytic effects of Salmonella typhosa vaccine in the rabbit, when mixed with rabbit plasma. LeQuire (4) confirmed this potentiation and showed that it was not abolished by prior treatment with hepaHn. Grant (5) found that the potentiation of pyrogenlc effect by plasma could not be demonstrated in ~nlmal~ rendered tolerant to endotoxin. Farret al. (6) confirmed that the pyrogenlc effect of endotoxin in rabbits was augmented by both human and rabbit plasma, and showed that the serum of tolerant animals failed to produce this augmentation. They believed this to be due to humoral inhibitors. All of these investigators were concerned with pyrogenic effects, and the amounts of human plasma and endotoxin utilized by Farr et al. (6) are too small to produce effects of the kind to be reported.

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