LETHAL SHOCK IS INDUCIBLE BY LIPOPOLYSACCHARIDE BUT NOT BY SUPERANTIGEN IN MICE WITH RETROVIRUS-INDUCED IMMUNODEFICIENCY SYNDROME

The retrovirus-induced murine AIDS (MAIDS) shares many features with h uman AIDS, Here, we examined the susceptibility of mice with MAIDS to staphylococcal enterotoxin-triggered shock. Following sensitization wi th D-galactosamine (D-Gal), mice with MAIDS were resistant to the othe rwise lethal effect of superantigen staphylococcal enterotoxin A (SEA) , Peak IL-2 levels in these mice after D-Gal/SEA challenge were 10-fol d higher than those in uninfected controls, and concurrently, IL-10 le vels rose markedly with reduction of circulating IL-1 and IFN-gamma. T reatment with neutralizing anti-IL-10 mAb before D-Gal/SEA challenge l ed to increased IFN-gamma levels in mice with MAIDS, and resulted in a dose-dependent mortality, In contrast, mice with MAIDS were more susc eptible to the toxicity of bacterial endotoxin LPS than were uninfecte d controls. Administration of 100 mu g LPS alone induced 50% lethality in mice infected with MAIDS virus 8 wk previously but not in uninfect ed controls, Administration of 10 mu g 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/m l in mice with MAIDS 4 h after LPS challenge. These results suggest th at aberrant profiles of cytokine production are crucial in determining fatal outcome in these two types of septic shock in MAIDS.