Compartmentalization of intravesical and systemic interleukin-6 and tumor necrosis factor α in mice stimulated with porins and lipopolysaccharide from Salmonella typhimurium

Abstract

Mucosal surfaces represent a natural colonization site for Gram-negative bacteria. We have already demonstrated the biologic role of Salmonella typhimurium porins in vitro and in vivo. In this paper we studied mucosal and systemic interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) production in systematically challenged mice or after intravesical administration of LPS or porins from S. typhimurium. It was found that serum IL-6 levels increased in BALB/c mice 4 h after receiving either i.v. LPS or porins from S. typhimurium. The porin challenge was stronger. Serum IL-6 levels were higher after porins than after LPS. IL-6 was not detected in the urine of i.v. challenged mice. Findings regarding IL-6 urine levels in intravesically treated mice were comparable. In porin-challenged mice they decreased more slowly than the LPS-challenged ones. IL-6 was not detected in the serum of intravesically challenged mice. In i.v. LPS-challenged mice, serum TNFα levels peaked earlier (at 2 h) than the IL-6 levels. A higher 2 h peak was instead seen in porin-challenged mice. TNFα was not detected in the urine of i.v. challenged mice. With intravesical LPS challenge, urinary TNFα levels peaked at 24 h, whereas in the porin-challenged mice the peak occurred 12 h earlier and was higher. Serum samples revealed no detectable TNFα. These findings confirm that both porins and LPS activate the mucosal response, without any systemic involvement, as, for example, in patients with diseases such as pyelonephritis or gastroenteritis.