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The Journal of Immunology, Vol 155, Issue 7 3494-3500, Copyright © 1995 by American Association of Immunologists

ARTICLES

Lethal shock is inducible by lipopolysaccharide but not by superantigen in mice with retrovirus-induced immunodeficiency syndrome

Y Aoki, K Hiromatsu, T Arai, J Usami, M Makino, H Ishida and Y Yoshikai
Laboratory of Host Defense, Nagoya University School of Medicine, Japan.

The retrovirus-induced murine AIDS (MAIDS) shares many features with human AIDS. Here, we examined the susceptibility of mice with MAIDS to staphylococcal enterotoxin-triggered shock. Following sensitization with D-galactosamine (D-Gal), mice with MAIDS were resistant to the otherwise lethal effect of superantigen staphylococcal enterotoxin A (SEA). Peak IL-2 levels in these mice after D-Gal/SEA challenge were 10- fold higher than those in uninfected controls, and concurrently, IL-10 levels rose markedly with reduction of circulating IL-1 and IFN-gamma. Treatment with neutralizing anti-IL-10 mAb before D-Gal/SEA challenge led to increased IFN-gamma levels in mice with MAIDS, and resulted in a dose-dependent mortality. In contrast, mice with MAIDS were more susceptible to the toxicity of bacterial endotoxin LPS than were uninfected controls. Administration of 100 micrograms LPS alone induced 50% lethality in mice infected with MAIDS virus 8 wk previously but not in uninfected controls. Administration of 10 micrograms LPS caused acute shock in D-Gal-sensitized mice with MAIDS. Peak TNF-alpha levels in these mice after LPS challenge were increased more than 10-fold, whereas IL-10 levels were one-third of those after SEA challenge. Moreover, serum IFN-gamma was undetectable in uninfected controls and rose to 1063 +/- 483 pg/ml in mice with MAIDS 4 h after LPS challenge. These results suggest that aberrant profiles of cytokine production are crucial in determining fatal outcome in these two types of septic shock in MAIDS.


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D. Liu, X. Y. Liu, D. Robinson, C. Burnett, C. Jackson, L. Seele, R. A. Veach, S. Downs, R. D. Collins, D. W. Ballard, et al.
Suppression of Staphylococcal Enterotoxin B-induced Toxicity by a Nuclear Import Inhibitor
J. Biol. Chem., April 30, 2004; 279(18): 19239 - 19246.
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