Potentiation of inhaled staphylococcal enterotoxin B-induced toxicity by lipopolysaccharide in mice.
Nonhuman primates are the established model for evaluating toxic responses to staphylococcal enterotoxins (SEs), as they react similarly to humans. Rodents are generally considered unresponsive to SEs. Binding affinities and T-cell reactivity suggest that SE binds more efficiently to primate major histocompatability complex class II receptors than to mouse receptors. We investigated the potentiation of staphylococcal enterotoxin B (SEB) inhalation toxicity by lipopolysaccharide (LPS) in BALB/c mice. Lethality occurred only when SEB was potentiated by LPS. Neither SEB nor LPS produced lethal effects alone. Temporal responses of interleukin 1 alpha, tumor necrosis factor alpha, interleukin 2, and interferon-gamma evoked by inhaled SEB were enhanced by LPS. By 24 hr after intoxication, serum cytokines decreased to baseline levels, and consistent pulmonary perivascular leukocytic infiltrates were evident histologically. Histologic lesions induced by inhalation exposure to SEB by mice, with or without potentiation by LPS, were similar to those in the rhesus monkey. Predominant pulmonary lesions included severe, diffuse interstitial and alveolar pulmonary edema, leukocytic infiltrates, mild perivascular edema, and alveolar fibrin deposition. Although the mechanism of aerosolized SEB-induced toxicity has not been completely resolved, similarities in histologic lesions, cytokine responses, and acute dose-response suggest the LPS-potentiated mouse model may be a credible alternative to the nonhuman primate model.
LeClaire
R D
RD
Toxinology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702-5011, USA.
Hunt
R E
RE
Bavari
S
S
Estep
J E
JE
Nelson
G O
GO
Wilhelmsen
C L
CL
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004768:Enterotoxins / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C
D004768:Enterotoxins; D008070:Lipopolysaccharides; C031818:enterotoxin B, staphylococcal