Exogenous cytokine modulation or neutralization of interleukin-10 enhance survival in lipopolysaccharide-hyporesponsive C3H/HeJ mice with Klebsiella infection

Immunology. 1999 Sep;98(1):90-7. doi: 10.1046/j.1365-2567.1999.00838.x.

Abstract

Klebsiella pneumoniae has been isolated from liver abscesses in patients with leukaemia or diabetes. The resistance of Klebsiella infection in lipopolysaccharide (LPS)-hyporesponsive mice is unclear. Female C3H/HeJ and C3H/HeN mice, 6-8 weeks old, were intraperitoneally (i.p.) injected with K. pneumoniae. The results showed that C3H/HeJ mice were 24 times more susceptible [lethal dose 50% (LD50) 250 colony-forming units] than C3H/HeN mice to K. pneumoniae infection. C3H/HeJ mice, uninfected or infected with K. pneumoniae, had higher liver interleukin (IL)-10 levels and IL-10 mRNA levels than C3H/HeN mice. Previously, pretreatment with IL-1beta and tumour necrosis factor-alpha (TNF-alpha) protected C3H/HeJ mice from lethal bacterial infection. Therefore the effects of pretreatment with IL-1beta and TNF-alpha or antimurine IL-10 antibody i.p. 1 hr before this infection in both strains of C3H mice were examined. Pretreatment with TNF-alpha or anti-IL-10 antibody enhanced the survival of both strains of mice. TNF-alpha, in combination with IL-1beta, enhanced the survival and bacterial clearance better than single pretreatment in C3H/HeJ mice. Anti-IL-10 antibody increased bacterial clearance and significantly reduced liver cytokine mRNA levels in C3H/HeJ mice more than it did in the controls during infection. These results indicate that exogenous cytokine modulation or neutralization of IL-10 enhance the resistance of LD50 infection in C3H/HeJ mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Colony Count, Microbial
  • Female
  • Immunotherapy
  • Interleukin-1 / therapeutic use
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Klebsiella Infections / immunology*
  • Klebsiella Infections / prevention & control
  • Klebsiella pneumoniae*
  • Lethal Dose 50
  • Lipopolysaccharides / immunology*
  • Liver / immunology*
  • Mice
  • Mice, Inbred C3H
  • RNA, Messenger / analysis
  • Statistics, Nonparametric
  • Tumor Necrosis Factor-alpha / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Interleukin-1
  • Lipopolysaccharides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10