Endogenous IL-10 leads to impaired bacterial clearance and reduced survival in a murine model of chronic peritonitis.
We previously observed insufficient neutrophil accumulation and a lack of TNF-alpha response at the site of infection until bacteria numbers >10(5) colony forming units in our model of chronic murine peritonitis, suggesting a defective host response after bacterial challenge with Klebsiella pneumoniae (Klebsiella). The aim of this study was to determine a potentially immunosuppressive effect of IL-10 in this model of chronic peritonitis. Balb/c animals were injected with 10(3) colony forming units Klebsiella intraperitoneally. Gentamicin (5 mg/kg/day BID) was given subcutaneously (s.c.) for two days and then withdrawn. Animals were treated with anti-IL-10 antibody or IgG isotype control (s.c.) before or after Klebsiella administration. Survival was determined over 14 days. Similarly treated animals were harvested after 48 h to obtain liver tissue, peritoneal fluid and blood. Bacteria and neutrophil counts were determined. TNF-alpha and IL-10 were measured by ELISA. Anti-IL-10 antibody significantly increased survival and bacterial clearance in the observed compartments. Anti-IL-10 administration did not lead to an increase in TNF-alpha concentrations or neutrophil accumulation at the site of infection at lower levels of Klebsiella. We conclude that endogenous IL-10 is detrimental for survival and bacterial clearance in this model of chronic peritonitis.
Veterans Affairs Medical Center-Louisville, Department of Surgery, University of Louisville, 550 South Jackson Street, Louisville, KY 40292, USA. amlenz01@gwise.louisville.edu
Andreas M
AM
Lenz
Glen A
GA
Franklin
Mark
M
Fairweather
Michael L
ML
McClintock
Venkatakrishna R
VR
Jala
James C
JC
Peyton
Sarah A
SA
Gardner
William G
WG
Cheadle
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005839:Gentamicins / Q000494:pharmacology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology*; D007710:Klebsiella Infections / Q000276:immunology*; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010538:Peritonitis / Q000276:immunology* / Q000382:microbiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000900:Anti-Bacterial Agents; D000906:Antibodies; D005839:Gentamicins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10