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 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.
Aoki
Y
Y
Laboratory of Host Defense, Nagoya University School of Medicine, Japan.
Hiromatsu
K
K
Arai
T
T
Usami
J
J
Makino
M
M
Ishida
H
H
Yoshikai
Y
Y
D000818:Animals; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology; D012769:Shock / Q000139:chemically induced* / Q000276:immunology / Q000401:mortality; D018089:Superantigens / Q000008:administration & dosage* / Q000276:immunology
D004768:Enterotoxins; D007375:Interleukin-1; D007376:Interleukin-2; D008070:Lipopolysaccharides; D018089:Superantigens; D016753:Interleukin-10; D007371:Interferon-gamma