Anti‐interferon‐γ antibody protects mice against the generalized Shwartzman reaction

Billiau, Alfons; Heremans, Hubertine; Vandekerckhove, F; Dillen, Chris

doi:10.1002/eji.1830171228

Cited by 87 publications

(38 citation statements)

References 16 publications

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“…The respective role of IFN-g and TNF-a in the development of generalized Shwartzman reaction has been reported by several groups. [23][24][25][26][27] IFN-g renders the mice more sensitive to the reaction and plays a regulatory role. On the other hand, TNF-a functions as an execution factor and causes systemic lethal shock in mice.…”

Section: Discussionmentioning

confidence: 99%

Lethal endotoxic shock using α-galactosylceramide sensitization as a new experimental model of septic shock

Ito

Koide

Hassan

et al. 2006

Laboratory Investigation

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The effect of a-galactosylceramide (a-GalCer) on lipopolysaccharide (LPS)-mediated lethality was examined. Administration of LPS killed all mice pretreated with a-GalCer, but not untreated control mice. The lethal shock in a-GalCer-sensitized mice was accompanied by severe pulmonary lesions with marked infiltration of inflammatory cells and massive cell death. On the other hand, hepatic lesions were focal and mild. A number of cells in pulmonary and hepatic lesions underwent apoptotic cell death. a-GalCer sensitization was ineffective for the development of the systemic lethal shock in Va14-positive natural killer T cell-deficient mice. Sensitization with a-GalCer led to the circulation of a high level of interferon (IFN)-c and further augmented the production of tumor necrosis factor (TNF)-a in response to LPS. The lethal shock was abolished by the administration of anti-IFN-c or TNF-a antibody. Further, the lethal shock did not occur in TNF-a-deficient mice. Taken together, a-GalCer sensitization rendered mice very susceptible to LPS-mediated lethal shock, and IFN-c and TNF-a were found to play a critical role in the preparation and execution of the systemic lethal shock, respectively. The LPS-mediated lethal shock using a-GalCer sensitization might be useful for researchers employing experimental models of sepsis and septic shock.

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Section: Discussionmentioning

confidence: 99%

Lethal endotoxic shock using α-galactosylceramide sensitization as a new experimental model of septic shock

Ito

Koide

Hassan

et al. 2006

Laboratory Investigation

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“…7 The role of IFN-g during in vitro LPS-challenge, 30 in vivo endotoxemia in mice, [16][17][18][19][20] or the generalized Shwartzman reaction in mice, 24,33,34 has been well established. Disseminated intravascular coagulation and shock associated with meningococcal sepsis are considered to be the clinical counterparts of the ''classical'' generalized Shwartzmann reaction.…”

Section: Interferon Gmentioning

confidence: 99%

Interleukin 12 Levels During the Initial Phase of Septic Shock With Purpura in Children: Relation to Severity of Disease

et al. 1997

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“…IL-12 and other ILs, in turn, activate NK and Th1 cells to produce IFN-␥ (36). Both TNF-␣ and IFN-␥ are proinflammatory cytokines involved in LPS-induced toxicity (37)(38)(39)(40). Reporting that IRF-1 plays an important role in the pathogenesis of disease models mediated by TNF and IFN-␥ is evidenced by experiments in IRF-1 Ϫ/Ϫ mice.…”

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confidence: 99%

Regulation of Lipopolysaccharide Sensitivity by IFN Regulatory Factor-2

Cuesta

Salkowski

Thomas

et al. 2003

The Journal of Immunology

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IFN regulatory factors (IRFs) are a family of transcription factors and include several members that regulate expression of pro- and anti-inflammatory genes. Mice with a targeted mutation in IRF-2 (IRF-2−/−) were studied after injection of LPS to evaluate the importance of IRF-2 in the regulation of endotoxicity. IRF-2−/− mice were highly refractory to LPS-induced lethality. Although hepatic TNF-α mRNA and circulating TNF-α were significantly elevated in LPS-challenged IRF-2−/− mice, levels of IL-1, IL-12, and IFN-γ mRNA and protein, as well as IL-6 protein, were significantly lower than levels seen in LPS-challenged IRF-2+/+ mice. IRF-2−/− mice were also more refractory to TNF-α challenge than were control mice, which was consistent with their diminished sensitivity to LPS, yet no significant difference in the mRNA expression of TNFRs was observed. IL-12Rβ2 mRNA levels from LPS-challenged IRF-2−/− mice were significantly different after 1, 6, and 8 h, suggesting that both diminished IL-12 and altered IL-12R expression contribute to the paucity of IFN-γ produced. IRF-2 knockout mice also failed to sustain LPS-inducible levels of IRF-1 and IFN consensus sequence binding protein mRNA expression, two transacting factors required for IL-12 transcription, perhaps as a result of diminished IL-1β, IL-6, and IFN-γ levels. Liver sections from IRF-2+/+ and IRF-2−/− mice were analyzed 6 h after a typically lethal injection of LPS. IRF-2−/− mice exhibited greater numbers of apoptotic Kupffer cells than did wild-type mice, suggesting a novel anti-apoptotic role for IRF-2. Collectively, these findings reveal a critical role for IRF-2 in endotoxicity, and point to a previously unappreciated role for IRF-2 in the regulation of apoptosis.

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Anti‐interferon‐γ antibody protects mice against the generalized Shwartzman reaction

Cited by 87 publications

References 16 publications

Lethal endotoxic shock using α-galactosylceramide sensitization as a new experimental model of septic shock

Lethal endotoxic shock using α-galactosylceramide sensitization as a new experimental model of septic shock

Interleukin 12 Levels During the Initial Phase of Septic Shock With Purpura in Children: Relation to Severity of Disease

Regulation of Lipopolysaccharide Sensitivity by IFN Regulatory Factor-2

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