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, Y. Yoshikai

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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-γ. Treatment with neutralizing anti- IL-10 mAb before D-Gal/SEA challenge led to increased IFN-γ 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 mg LPS alone induced 50% lethality in mice infected with MAIDS virus 8 wk previously but not in uninfected controls. Administration of 10 μg LPS caused acute shock in D- Gal-sensitized mice with MAIDS. Peak TNF-α 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-γ was undetectabie 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.

Original languageEnglish
Pages (from-to)3494-3500
Number of pages7
JournalJournal of Immunology
Volume155
Issue number7
Publication statusPublished - Jan 1 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology

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