COMPARTMENTALIZATION OF INTRAVESICAL AND SYSTEMIC INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR-ALPHA IN MICE STIMULATED WITH PORINS AND LIPOPOLYSACCHARIDE FROM SALMONELLA-TYPHIMURIUM

Mucosal surfaces represent a natural colonization site for Gram-negati ve bacteria, We have already demonstrated the biologic role of Salmone lla typhimurium porins in vitro and in vivo. In this paper we studied mucosal and systemic interleukin-6 (IL-6) and tumor necrosis factor al pha (TNF alpha) production in systematically challenged mice or after intravesical administration of LPS or porins from S. typhimurium. It w as found that serum IL-6 levels increased in BALB/c mice 4 h after rec eiving either i.v. LPS or porins from S. typhimurium. The porin challe nge was stronger, Serum IL-6 levels were higher after porins than afte r LPS, IL-6 was not detected in the urine of i.v. challenged mice. Fin dings regarding IL-6 urine levels in intravesically treated mice were comparable, In porin-challenged mice they decreased more slowly than t he LPS-challenged ones, IL-6 was not detected in the serum of intraves ically challenged mice, In i.v. LPS-challenged mice, serum TNF alpha l evels peaked earlier (at 2 h) than the IL-6 levels, A higher 2 h peak was instead seen in porin-challenged mice, TNF alpha was not detected in the urine of i.v. challenged mice, With intravesical LPS challenge, urinary TNF alpha levels peaked at 24 h, whereas in the porin-challen ged mice the peak occurred 12 h earlier and was higher, Serum samples revealed no detectable TNF alpha. These findings confirm that both por ins and LPS activate the mucosal response, without any systemic involv ement, as, for example, in patients with diseases such as pyelonephrit is or gastroenteritis.