Mechanisms of endotoxin tolerance. The role of the spleen.

Greisman, Sheldon E.; Young, Edward J.; Workman, Joseph; Ollodart, Robert; Hornick, Richard B.

doi:10.1172/jci108242

Cited by 33 publications

(33 citation statements)

References 29 publications

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“…[15,16,24]. As the intervals of time between endotoxin challenge are lengthened, the cellular refractory state wanes and resistance then is dependent upon circulating antibodies which assist in endotoxin clearance [15,16,24]. Although antibody studies were not included in the present studies, the patterns of tolerance exhibited by animals injected with endotoxins of V. parahaemolyticus are in agreement with observations of others, and it would be anticipated that the continuous infusion with endotoxins would prevent emergence of antibody.…”

Section: Resultssupporting

confidence: 68%

“…Typical biphasic fever curves characteristic of the rabbit responses to endotoxin [15,16] are seen. Pyrogenicity of both preparations was retained following heating at 100 C for 1 hr.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Tolerance and Other Biological Properties of Vibrio parahaemolyticus Endotoxins

Sochard

Colwell

1976

Japanese Journal of Microbiology

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Biological properties of endotoxins prepared from three strains of Vibrio parahaemolyticus were compared with reference to commercially prepared Salmonella typhi endotoxin. Endotoxin assays performed in rabbits included dermal Shwartzman reactivity, pyrogenicity, heat stability, and ability to induce tolerance as well as cross-tolerance.Mice were used for endotoxin LD50 determinations. Results showed V. parahaemolyticus endotoxins were similar to that of S.typhi strain 0901.Induction of tolerance to V. parahaemolyticus strain 11590 endotoxin resulted in complete cross-tolerance to S. typhi endotoxin, and vice versa. Partial cross-tolerance to S. typhi endotoxin was demonstrated with rabbits rendered tolerant to endotoxin from V. parahaemolyticus strains Sak-3 and FC 1011. Absorption spectra, nitrogen, phosphorus and carbohydrate analyses revealed additional similarities between endotoxins from V. parahaemolyticus and endotoxin from a member of the Enterobacteriaceae.Known in Japan for two decades as a causative agent of large outbreaks of seafoodassociated poisoning, Vibrio parahaemolyticus has recently been found associated with similar outbreaks in the U.S.A. [1,4,7,8,14,26,40,42,43], and other countries [2,3]. Nevertheless, the mode of pathogenesis of V. parahaemolyticus is poorly understood. Strains isolated from clinical specimens and displaying hemolysis on selected media (Kanagawa-phenomenon positive) are considered to be enteropathogenic [30,39,49], whereas nonhemolytic (Kanagawa-phenomenon negative) seafood or seawater isolates are generally considered non-enteropathogenic [19,37,38]. The problem is further complicated by the frequent isolation of several different serotypes of V. parahaemolyticus during an outbreak of food poisoning [7,8].Biologically active components (hemolysins) from selected strains of V.parahaemolyticus have been isolated which do not, however, account for the spectrum of gastroenteritis symptoms observed in clinical cases [12,17,19,25,28,29,31,36,50,51]. A single case of endotoxin shock and leg gangrene due to infections by V. parahaemolyticus following an attack of gastroenteritis has been demonstrated [36].Endotoxins from V.parahaemolyticus have not previously been studied, although some chemical analyses ofO antigens [44,45] and K antigens have been reported [32,33]. The purpose of this research was to study the biological properties of V.parahaemolyticus endotoxins and to determine if they are similar to endotoxins classically prepared from selected members of the Enterobacteriaceae, such as Salmonella typhi.

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Section: Resultssupporting

confidence: 68%

“…Typical biphasic fever curves characteristic of the rabbit responses to endotoxin [15,16] are seen. Pyrogenicity of both preparations was retained following heating at 100 C for 1 hr.…”

Section: Resultsmentioning

confidence: 99%

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Tolerance and Other Biological Properties of Vibrio parahaemolyticus Endotoxins

Sochard

Colwell

1976

Japanese Journal of Microbiology

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“…Classically, low doses of the TLR4 agonist LPS, desensitize the host to subsequent endotoxin stimulation, a phenomenon known as endotoxin tolerance (11,12). This desensitization property has been described with other TLR agonists (13) and will be referred to as tolerance in this study.…”

mentioning

confidence: 78%

Prevention of autoimmune disease by induction of tolerance to Toll-like receptor 7

Hayashi¹,

Gray²,

Chan³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

101

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Activation of Toll-like receptors (TLR) contributes to the initiation and maintenance of chronic inflammation in autoimmune diseases, yet repeated exposure to a TLR agonist can induce hyporesponsiveness to subsequent TLR stimulation. Here, we used a synthetic TLR7 agonist, 9-benzyl-8-hydroxy-2-(2-methoxyethoxy) adenine (SM360320, 1V136) to study TLR7 induced attenuation of inflammatory responses and its application to autoimmune diseases. Repeated low dose administration of this TLR7 agonist induced hyporesponsiveness or tolerance to TLR2, -7, and -9 activators and limited the course of neural inflammation in an experimental allergic encephalomyelitis model. The hyporesponsiveness did not depend on T or B lymphocytes, but did require bone marrow derived cells. In addition, TLR7 tolerance reduced inflammation in a passive antibody mediated arthritis model. TLR7 tolerance did not cause global immunosuppression, because susceptibility to Listeria monocytogenes infection was not altered. The mechanism of TLR7 tolerance involved the up-regulation of 2 inhibitors of TLR signaling: Interleukin 1 Receptor Associated Kinase (IRAK) M, and Src homology 2 domain-containing inositol polyphosphate phosphatase (SHIP)-1. These findings suggest that induction of TLR7 tolerance might be a new therapeutic approach to subdue inflammation in autoimmune diseases.arthritis ͉ encephalomyelitis ͉ synthetic agonist

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“…Endotoxin tolerance has been divided into an early, non-immunological phase and a later immunological phase in which circulating antibodies might play a significant role in endotoxin detoxification (12,13). Based on literature data, we hypothesized that LPS tolerance produces an "adaptation" of the innate immune response (1).…”

Section: Discussionmentioning

confidence: 99%