LPS pretreatment by the oral route protects against sepsis induced by cecal ligation and puncture. Regulation of proinflammatory response and IgM anti-LPS antibody production as associated mechanisms

Objective: To explore the efficacy of prophylactic oral lipopolysaccharide (LPS) in sepsis induced by cecal ligation and puncture (CLP). Material: Male Balb/c mice. LPS serotype O55: B5 Treatment: Mice were treated every 4 days for a total of 5 times with 50 μg of LPS by intraperitoneal (IP) or oral (O) routes. Treatment was stopped one week prior to CLP. Control (C) groups received the vehicle orally, and sham (S) groups were used as reference. Methods: Histopathology was performed to determine inflammation in liver and lung. Serum cytokines were measured by ELISA, and TNFα tissue expression by RTPCR. Antibodies against LPS were measured by ELISA. Results: Administration of LPS by the oral route significantly increased survival (p<0.05) of mice in association with a reduction of Kupffer cells in liver, pulmonary edema in lung, shorter or delayed TNFα expression in target organs, a trend to decreased IFNγ and increased IL-10 serum levels, and a notable increase in the production of specific IgM anti-LPS antibodies. Conclusions: LPS by oral route protected against CLP. The underlying mechanisms could be the modulation of the proinflammatory response and an increased production of IgM anti-LPS antibodies. Received 12 July 2006; returned for revision 16 November 2006; returned for final revision 14 April 2007; accepted by I. Ahnfelt-R?nne 16 May 2007