Exogenous cytokine modulation or neutralization of interleukin-10 enhance survival in lipopolysaccharide-hyporesponsive C3H/HeJ mice with Klebsiella infection.
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.
Wang
M
M
Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Jeng
K C
KC
Ping
L I
LI
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015169:Colony Count, Microbial; D005260:Female; D007167:Immunotherapy; D007375:Interleukin-1 / Q000627:therapeutic use; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D007710:Klebsiella Infections / Q000276:immunology* / Q000517:prevention & control; D007711:Klebsiella pneumoniae; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000276:immunology*; D008099:Liver / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000032:analysis; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10