Interleukin-10 repletion suppresses pro-inflammatory cytokines and decreases liver pathology without altering viral replication in murine cytomegalovirus (MCMV)-infected IL-10 knockout mice

Yajarayma J. Tang-Feldman, G. Raymond Lochhead, Stephanie R. Lochhead, Cindy Yu, Claire Pomeroy

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Objective and design: To determine the role of interleukin-10 (IL-10) in protecting against the deleterious pro-inflammatory cytokine response to murine cytomegalovirus (MCMV), we studied the impact of IL-10 repletion in MCMV-infected IL-10 knockout (KO) mice. Materials and methods: IL-10 KO mice were infected with a sub-lethal dose of MCMV and treated daily with 5 μg of mouse recombinant IL-10 (mrIL-10). Cytokine transcription, viral load, cytokine expression and liver histopathology were assessed in IL-10 treated and untreated mice. Results: mrIL-10 repletion suppressed the exaggerated pro-inflammatory cytokine response observed in IL-10 KO mice (vs. control) both systemically and at the organ level, without affecting viral load. Levels of IFN-γ and TNF-α mRNA in livers of treated mice were ~50-70-fold lower than in untreated mice at day 5 post-infection (p ≥ 0.05). In spleens and sera, levels of IFN-γ and IL-6 were significantly lower in treated mice than in untreated mice at day 5-7 post-infection (p ≥ 0.05). IL-10 blunting of cytokine responses was accompanied by attenuation of inflammation in livers of treated mice. Conclusions: Repletion of IL-10 modulates the exaggerated pro-inflammatory cytokine responses that characterize IL-10 KO mice and protects against liver damage without altering viral load. IL-10 may be useful to control dysregulated pro-inflammatory cytokines responses during CMV infection.

Original languageEnglish (US)
Pages (from-to)233-243
Number of pages11
JournalInflammation Research
Volume60
Issue number3
DOIs
StatePublished - Mar 2011

Keywords

  • IL-10
  • IL-10 deficient
  • MCMV
  • Pro-inflammatory cytokines
  • Repletion
  • Viral load

ASJC Scopus subject areas

  • Pharmacology
  • Immunology

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