Central roles for IL-2 and MCP-1 following intranasal exposure to SEB: A new mouse model

Rapamycin Protects Mice from Staphylococcal Enterotoxin B-Induced Toxic Shock and Blocks Cytokine ReleaseInVitroandIn Vivo

“…There were 2 h of elapsed time between the first intranasal dose of 5 g SEB/mouse and the second i.p. dose of 2 g SEB/mouse, as this was the optimal time and dose previously determined to cause toxic shock without the use of synergistic agents (22). Mice exposed to both doses of SEB succumbed to death between 96 and 120 h, and lethal endpoints were recorded up to 168 h after the first toxin dose.…”

“…All efforts adhered to principles stated in the Guide for Care and Use of Laboratory Animals (37a). Previous results indicated the optimal timing for serum cytokine collection after mice were given a dual dose of SEB (22). Sera were collected from anesthetized mice by cardiac puncture at 5 and 24 h after SEB exposure.…”

“…Staphylococcal enterotoxin B (SEB) and the distantly related toxic shock syndrome toxin 1 are also called superantigens because they induce massive proliferation of T cells (29). In vitro and in vivo studies show that these superantigens induce high levels of various proinflammatory cytokines, and these potent mediators cause lethal shock in animal models (1,6,22,27,37,39,45,51,55). SEB also causes food poisoning (4, 21, 52) and is a potential bioterrorism threat agent, as humans are extremely sensitive to this superantigen, especially by inhalation (28).…”

“…The therapeutic efficacy of rapamycin in SEB-induced toxic shock was investigated by using a lethal murine model with intranasal delivery of SEB (22). This "double-hit" murine model relies on two low doses of SEB without the use of sensitizing agents such as lipopolysaccharide (LPS) or galactosamine to induce lethal shock (6,27,33,37,45).…”

CD1d-Independent Activation of Invariant Natural Killer T Cells by Staphylococcal Enterotoxin B through Major Histocompatibility Complex Class II/T Cell Receptor Interaction Results in Acute Lung Injury

“…Such mice died within 96 to 120 h while exhibiting severe lung injury. These studies suggested that while mice are more resistant to SEB, they can develop severe lung inflammation and die following exposure to relatively low concentrations of SEB through the intranasal route (10,13). Thus, the binding of MHC-II to SEB may not be the sole cause of increased resistance to SEB seen in mice.…”