Effect of tumor necrosis factor-alpha on infection with Salmonella typhimurium in a mouse model

Mice, inoculated with Salmonella typhimurium, either intraperitoneally (i.p.) or intragastrically (i.g.), developed a systemic infection with a high death rate within a few days after inoculation. Pretreatment of the mice with moderate concentrations of i.p. administered TNF-alpha 24 h before the administration of bacteria reduced the establishment of intracellular infection in the intestinal epithelial cells, and development of bacteremia. The mortality rate was reduced, and the survival time was extended by the same treatment. This effect of TNF-alpha was more pronounced against i.g. than against i.p. inoculated bacteria. The effect was dose dependent, thus concentrations above or below the optimal dose had less effect. No synergistic effect was seen if TNF-alpha was given in combination with interferon-gamma. These results indicate, that TNF-alpha may have a physiological effect in the host defence against facultatively intracellular Gram-negative bacteria.