Critical timing, location and duration of glucocorticoid administration rescue mice from superantigen-induced shock and attenuate lung injury.
Bacterial superantigens, such as staphylococcal enterotoxin B (SEB), are major virulence factors implicated in the pathogenesis of toxic shock. In this study we investigated the efficacy of glucocorticoid therapy in preventing SEB-induced lethal shock initiated through the respiratory route in mice. Dexamethasone, a potent anti-inflammatory steroid, administrated intranasally on the first day, followed by intraperitoneal doses on the subsequent 4 days, was effective in attenuating SEB-induced hypothermia, and reduction in systemic and pulmonary proinflammatory mediator release. This optimal dosing and schedule of glucocorticoid treatment mitigated lung inflammation and resulted in 100% survival in this intranasal mouse model of SEB-mediated shock.
Krakauer
Teresa
T
Integrated Toxicology Division, USAMRIID, Fort Detrick, MD 21702-5011, USA. teresa.krakauer@amedd.army.mil
Buckley
Marilyn J
MJ
Huzella
Louis M
LM
Alves
Derron A
DA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D016207:Cytokines / Q000097:blood; D003907:Dexamethasone / Q000008:administration & dosage*; D004333:Drug Administration Routes; D004768:Enterotoxins / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013210:Staphylococcus / Q000276:immunology*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004768:Enterotoxins; C031818:enterotoxin B, staphylococcal; D003907:Dexamethasone