Administration of interleukin-10 at the time of priming protects Corynebacterium parvum-primed mice against LPS- and TNF-alpha-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 with Corynebacterium parvum (Proprionibacterium acnes). We have extended our studies with IL-10 in C. parvum-primed mice and in some cases have observed protection that appears to depend on the strength of the sensitization to C. 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-alpha. In addition, the mice were protected against LPS- and TNF-alpha-induced lethality with a single dose of an anti-TNF-alpha or anti-IFN-gamma mAb given at the time of priming. Our results suggest that TNF-alpha and IFN-gamma are produced early after priming with C. parvum and are at least partly responsible for the enhanced sensitivity of the mice to LPS and TNF-alpha. IL-10 affords protection to the mice because of its ability to block the C. parvum-induced TNF-alpha and IFN-gamma responses.

• Authors: S R Smith, C Terminelli, G Denhardt, S Narula, G J Thorbecke
• Journal: Cellular immunology (Cell Immunol) Vol. 173 Issue 2 Pg. 207-14 (Nov 01 1996) ISSN: 0008-8749 [Print] Netherlands
• PMID: 8912878 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Cytokines
• Lipopolysaccharides
• Recombinant Proteins
• Tumor Necrosis Factor-alpha
• Interleukin-10

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, immunology)
• Cytokines (biosynthesis)
• Endotoxemia (prevention & control)
• Humans
• Immunization
• Interleukin-10 (immunology, pharmacology)
• Lipopolysaccharides (antagonists & inhibitors, toxicity)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Propionibacterium acnes (immunology)
• Recombinant Proteins (pharmacology)
• Splenomegaly (immunology)
• Time Factors
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, immunology, toxicity)