IL-10 production during endotoxic shock is part of a protective mechan
ism that involves IL-10-induced inhibition of TNF synthesis. We sought
to determine the role of IL-10 in septic peritonitis induced by cecal
ligation and puncture (CLP). CLP led to a rapid induction of IL-10 mR
NA in various organs of C57Bl/6 mice. Ih liver, IL-10 mRNA was detecta
ble within 1 h following CLP, while in spleen and lungs, IL-10 mRNA wa
s detected from 2 to 4 h and onward. IL-10 protein became detectable i
n plasma 2 h after CLP, reaching peak concentrations after 12 h (12.7
+/- 5.7 ng/ml). Pretreatment (-2 h) with anti-IL-l0 mAb resulted in hi
gher plasma TNF levels following CLP when compared with mice treated w
ith control mAb. Plasma IL-l activity and IFN-gamma remained undetecta
ble in virtually all mice. Anti-IL-10 enhanced mortality after CLP (p
< 0.05 by log-rank test). Addition of anti-TNF mAb did not influence t
he increased mortality associated with anti-IL-10 treatment. Septic pe
ritonitis is associated with sustained production of IL-10 in various
organs, which serves to protect the host against lethality.