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.