The Role of Endotoxin during Typhoid Fever and Tularemia in Man. III. Hyperreactivity to Endotoxin during Infection *

Greisman, Sheldon E.; Hornick, Richard B.; Woodward, Theodore E.

doi:10.1172/jci105049

Cited by 26 publications

(15 citation statements)

References 14 publications

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“…with the Brucella preparation (32,33), systemic hyperreactivity waned rapidly during convalescence from typhoid fever and tularemia with the purified endotoxin preparations employed in the present studies (4). Alternative attempts to demonstrate increases in cytophilic antibody capable of sensitizing leukocytes to the injurious activity of bacterial endotoxin, as has been reported in the chicken during S. galliniaruin infection (18), were also unsuccessful.…”

Section: Discussionmentioning

confidence: 73%

“…It has already been demonstrated that the phenomenon is not a nonspecific reaction to fever per se; the hyperreactivity was detectable during the afebrile incubation period and continued into the afebrile convalescent phase; moreover, volunteers febrile with the virus of Sandfly fever exhibited no detectable hyperreactivity (4 Raskova (30). Removal of natural protective circulating factors or enhancement of cellular reactivity by subfebrile levels of endotoxemia also appears an unlikely mechanism of hyperreactivity, since infusions of endotoxin for up to 40 hr at rates that just failed to elicit 10 Unpublished observations.…”

Section: Discussionmentioning

confidence: 98%

“…This demonstration was complicated by the remarkable enhancement of pyrogenic and subjective toxic reactivity to homologous and heterologous (S. typhosa and Pseudomonas) endotoxins induced by the infectious diseases. Such augmented responsiveness was probably first encountered in man during attempts to treat typhoid fever with S. typhosa and E. coli vaccines in the preantibiotic era (20)(21)(22), but controlled studies proving hyperreactivity have only recently been carried out (4 for all doses of endotoxins tested, but that the dose-response relationships also become appreciably steeper during illness. In those volunteers rendered tolerant to the pyrogenic activity of the endotoxins before induction of typhoid fever, hyperreactivity during illness though present was detectably blunted, i.e., the pyrogenic tolerance mechanisms, activated before illness, continued to operate within the framework of the hyperreactive state.…”

Section: Discussionmentioning

confidence: 99%

“…This hyperreactivity occurred regardless of whether a high degree of tolerance was preinduced by repeated daily intravenous injections of endotoxin before infection, or whether only a single control intravenous base line test was performed. It was emphasized that it was uncertain as to whether this hyperreactivity to endotoxin involved the inhibition of those mechanisms that participate in tolerance, or whether the tolerance mechanisms remained functional and offered some partial protection (4). The effect of sustained endotoxin infusions during illness was not determined.…”

Section: Introductionmentioning

confidence: 99%

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The role of endotoxin during typhoid fever and tularemia in man

Greisman¹,

Hornick²,

Wagner³

et al. 1969

J. Clin. Invest.

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A B S T R A C T Volunteers infected with Salmonella ty-phosa develop a remarkable hyperreactivity to the pyrogenic and subjective toxic activities of homologous (S. typhosa) and heterologous (Pseudomonas) endotoxins. The present studies quantitate this augmented reactivity and demonstrate by three differing approaches that significant tolerance to these endotoxins can be readily induced within the framework of the hyperreactive state. Thus, (a) tolerance induced before illness by repeated daily intravenous injections of the endotoxins remained demonstrable during overt illness, (b) daily intravenous injections of the endotoxins begun during overt illness evoked progressively increasing tolerance, and (c) continuous intravenous infusions of S. typhosa endotoxin during illness rapidly induced a pyrogenic refractory state. Despite unequivocal activation of the endotoxin tolerance mechanisms by any of the above methods, the febrile and toxic course of typhoid fever proceeded unabated. Similarly, in other volunteers with Pasteurella tularensis infection, continuous intravenous infusions of S. typhosa endotoxin evoked initial hyperreactive febrile and subjective toxic responses followed by rapid appearance of a pyrogenic refractory state without modification of the underlying clinical illness. These observations suggest that circulating endotoxin plays no major role in pathogenesis of the sustained fever and toxemia during typhoid fever and tularemia in man. The mechanisms responsible for the systemic hyperreactivity to endotoxin during typhoid fever and tularemia were further investigated. Low grade endotoxemia, nonspecific effects of tissue injury, impaired ability of the reticuloendothelial system to clear circulating endotoxin, and production of cytophilic antibodies capable of sensitizing leukocytes to endotoxin did not appear responsible. Inflammatory reactions to intradermal S. typhosa endotoxin increased significantly during typhoid fever. However, since no such dermal hyperreactivity developed to Pseudomonas endotoxin during typhoid fever nor to S. typhosa endotoxin during tularemia, the systemic hyperreactivity to bacterial endotoxins during typhoid fever and tularemia could not presently be ascribed to enhanced levels of acquired hypersensitivity.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The role of endotoxin during typhoid fever and tularemia in man

Greisman¹,

Hornick²,

Wagner³

et al. 1969

J. Clin. Invest.

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“…In volunteer experiments, patients were made tolerant of endotoxin by repeated injection of small doses to the extent that they could tolerate 2.5 µg with no ill effect. In spite of this the volunteers became ill when challenged with S. typhi, exhibiting the characteristic clinical features of the disease (Greisman, Hornick and Woodward, 1964). Like other members of the Enterobacteriaceae, S. typhi and other salmonellas possess a LPS with a lipid A core.…”

Section: The Virulence Of S Typhimentioning

confidence: 99%