Administration of Interleukin-10 at the Time of Priming ProtectsCorynebacterium parvum-Primed Mice against LPS- and TNF-α-Induced Lethality

Abstract

Several laboratories have described the protective effects of interleukin-10 (IL-10) in mouse models of lethal endotoxemia. In most of these experiments, protection was observed in normal mice that were given a lethal dose of LPS. However, we failed to observe protection with IL-10 in LPS-challenged mice that had been primed withCorynebacterium parvum(Proprionibacterium acnes). We have extended our studies with IL-10 inC. parvum-primed mice and in some cases have observed protection that appears to depend on the strength of the sensitization toC. parvum.When IL-10 was administered to mice at the time of priming, it was particularly effective in blocking sensitization, as evidenced by the inability of treated mice to mount a strong inflammatory cytokine response when subsequently challenged with LPS. Following such treatment with IL-10,C. parvum-primed mice were also protected from a subsequent lethal challenge with rMuTNF-α. In addition, the mice were protected against LPS- and TNF-α-induced lethality with a single dose of an anti-TNF-α or anti-IFN-γ mAb given at the time of priming. Our results suggest that TNF-α and IFN-γ are produced early after priming withC. parvumand are at least partly responsible for the enhanced sensitivity of the mice to LPS and TNF-α. IL-10 affords protection to the mice because of its ability to block theC. parvum-induced TNF-α and IFN-γ responses.