Studies With Brucella Endotoxin in Humans: The Significance of Susceptibility to Endotoxin in the Pathogenesis of Brucellosis

Abernathy, Robert S.; Spink, Wesley W.

doi:10.1172/jci103601

Cited by 52 publications

(22 citation statements)

References 11 publications

(11 reference statements)

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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: 80%

“…An alternative hypothesis for the systemic hyperreactivity to endotoxin during typhoid fever and tularemia would be that suggested by Abernathy and Spink for the hyperreactivity to Brucella endotoxin during brucellosis, i.e., acquired hypersensitivity (32,33). Important support for this hypothesis was derived from the apparent correlation between the intensity of the dermal inflammatory responses elicited by brucella skin test antigens and the intensity of the pyrogenic and toxic systemic responses to Brucella endotoxin (32).…”

Section: Discussionmentioning

confidence: 99%

“…Important support for this hypothesis was derived from the apparent correlation between the intensity of the dermal inflammatory responses elicited by brucella skin test antigens and the intensity of the pyrogenic and toxic systemic responses to Brucella endotoxin (32). However, the Brucella endotoxin preparation employed by Abernathy and Spink possessed pyrogenic activities quite different from those of classical purified preparations."'…”

Section: Discussionmentioning

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: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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 eleven patients the picture resembled an undulant type of fever; the interval between the two waves varying from 2 to 9 months and in two the illness during the second wave was more severe than during the first. It is suggested that these examples might support the view that sensitization of the body to the brucella endotoxin is of importance in the pathogenesis of brucellosis (Spink & Anderson, 1954;Abernethy & Spink, 1958).…”

Section: Infection Among the Villagersmentioning

confidence: 76%

A village epidemic of brucellosis

et al. 1961

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A village epidemic of brucellosis, due to Brucella melitensis, contracted from infected sheep and goats owned by the vifiagers is described. Of the 309 inhabitants eighty-four became infected and seventy-nine were clinically ill with brucellosis. The investigation covered 232 of the total population and nearly all those not examined belonged to the age group, 0–5 years, not directly exposed to infection by contact with diseased animals.The population of the village was made up of forty-six families, only nine of which escaped infection. In the affected families, the incidence varied from one to seven in each case. The size of the family varied from three to eleven but there was no correlation between the size of the family and the number contracting brucellosis, neither did sex play any part in the incidence. All age groups were susceptible but the morbidity increased with age and this was correlated with increased risk of exposure to infection of the older age groups.There was considerable variation in the severity of the clinical illness but there were no fatiities and all patients responded to antibiotic therapy.Brucella melitensis was isolated from twenty-eight of the thirty-six patients subjected to blood culture and specific agglutinins at an acceptable level were demonstrated in all but three of those with a clinical illness.The number of persons without evidence of clinical brucellosis who possessed significant brucella agglutinins was very small and the assumption that in an endemic area the number of infected persons is much greater than the number clinically ill was not borne out in the outbreak described here.Persistence of specific agglutinins up to 2 years after recovery from the clinical illness is recorded.We wish to pay tribute to the late Professor J. Gurevitch for his constant interest and helpful advice.Thanks are due to Prof. M. Ruiz Castaneda for providing us with the Castaneda bottles for blood culture work, to Dr E. Neeman of the Government Brucella Reference Laboratory for supplying the Standard Brucella Antigen and for examining the strains of Brucella isolated, and to Colonel H. J. Bensted for his interest and help in preparing the paper. Finally, we are indebted to Mrs Aliza Abut Kayner, social worker in the village health centre, for her valuable help in gathering statistical data.

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“…In man, increased reactivity to the pyrogenic activity of Brucella endotoxin has been established during active brucellosis (16). Specific hypersensitivity induced by the infection was suggested as the mechanism underlying such hyperreactivity to the Brucella endotoxin.…”

Section: Resultsmentioning

confidence: 99%