TREATMENT OF MICE WITH STAPHYLOCOCCAL-ENTEROTOXIN-B ENHANCES RESOLUTION OF AN INDUCED ESCHERICHIA-COLI URINARY-TRACT INFECTION AND STIMULATES PRODUCTION OF PROINFLAMMATORY CYTOKINES

Staphylococcal enterotoxin B (SEE) is a superantigen that causes mass proliferation of murine V beta 8(+) T cells via major histocompatibili ty complex (MHC) class II molecules and leads to their apoptosis or an ergy, SEE also stimulates other MHC class II-bearing cells to prolifer ate and secrete cytokines, some of which might enhance early host defe nses against urinary tract infections (UTIs), We investigated the effe ct of SEE administration on the course of an induced Eseherichia coli UTI in mice, Treatment with SEE 3 or 7 days before the infection had n o effect on UTI resolution, However, when SEE was administered at the time of infection, bacterial colonization in the bladders was reduced at time points between 6 h and 3 days. This reduction was not due to a physiological effect, such as increased urinary glycosaminoglycans, o r altered pH, nor was SEE bactericidal for the inoculum, Cytokine prod uction in the spleens and bladders of SEE-treated and/or infected mice was evaluated by reverse transcription-PCR, SEE treatment resulted in increased levels of interleukin-2 (IL-2),IL-4, IL-6, and IL-10 mRNAs in the spleen and IL-1 alpha, IL-6, granulocyte-macrophage colony-stim ulating factor, and tumor necrosis factor alpha transcripts in the bla dder, Also, liver cells from SEE-treated mice expressed IL-6 mRNA,whic h induces the production of acute-phase proteins, These data indicate that SEE treatment in vivo leads to enhanced UTI resolution through a mechanism that may include direct stimulation of effector cells in the bladder, the action of cytokines induced in the spleen, or cytokine-m ediated induction of acute-phase proteins.