Nitric oxide participates in the recovery of normal jejunal epithelial iontransport following exposure to the superantigen, Staphylococcus aureus enterotoxin B

Bacterial superantigens (SAgs) are potent T cell activators. Mice treated 4 h previously with the SAg, Staphylococcus aureus enterotoxin B (SEB), disp lay reduced ion transport (assessed by short circuit current) responses to prosecretory stimuli, which normalize 24 h posttreatment, Here, mice were t reated with SEB alone or in combination with an inhibitor of the inducible form of NO synthase (iNOS), L-NIL. Subsequently, jejunal iNOS expression wa s detected by immunohistochemistry, ion transport was evaluated in Ussing c hambers, and serum levels of TNF-alpha and IFN-gamma were measured by ELISA . SEB-treated mice had increased epithelial iNOS immunoreactivity, and nume rous iNOS-positive CD3(+) T cells occurred in their mucosa and submucosa. C oncomitant treatment with L-NIL did not affect the reduced short circuit cu rrent responsiveness to electrical nerve stimulation or the prosecretory ag ents, carbachol and forskolin, that occurred 4 h post-SEB (5 mu g) treatmen t. However, Isc responses in L-NIL-plus SEE-treated mice mere still signifi cantly reduced 24 h posttreatment, indicating a role for NO in the restorat ion of normal ion transport following exposure to SAgs, The prolongation of epithelial ion transport abnormalities correlated with elevated serum leve ls of TNF-alpha and IFN-gamma in mice treated 24 h previously with L-NIL pl us SEB compared with those in controls and SEB-only-treated mice. Additiona lly, mice treated with L-NIL plus SEB and TNF-alpha- or IFN-gamma-neutraliz ing Abs displayed normal jejunal ion transport characteristics 24 h posttre atment. We conclude that NO mobilization is important in the homeostatic re covery response following immune stimulation by SAgs and that the beneficia l effect of NO in this model system is probably via regulation of TNF-alpha and IFN-gamma production.