Treatment of mice with IL-1 before infection increases resistance to a lethal challenge with Salmonella typhimurium. The effect correlates with the resistance allele at the Ity locus

Abstract

Administration of a single dose of IL-1 alpha to various strains of mice approximately 16 h before a lethal infection with Salmonella typhimurium resulted in a significant augmentation of survival in most Ityr, but in no Itys strains of mice. Lower numbers of bacteria were observed in the liver and spleen in response to IL-1 pretreatment shortly after infection in all Ityr strains of mice tested, including the congenic C.D2-Ityr mice. Treatment with IL-1 alpha after infection had no effect on survival in either Ityr or Itys mice. A combination of IL-1 alpha pretreatment with IL-1 alpha post-treatment did not increase survival over the effect of IL-1 alpha pretreatment alone in Ityr mice and did not increase the survival of the Itys mice. The combination of IL-1 alpha pretreatment with GM-CSF post-treatment was effective in Ityr but not in Itys strains of mice. Thus, IL-1 alpha pretreatment enhances the resistance of Ityr, but not Itys strains of mice to a lethal challenge with S. typhimurium by up-regulating antibacterial mechanisms shortly after infection.