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Aged IRF3-KO Mice are Protected from Sepsis.

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Interferon regulatory factor 3 (IRF3) worsens sepsis outcomes in aged mice. IRF3 knockout mice showed significantly improved survival and reduced disease severity in a sepsis model, highlighting IRF3 as a therapeutic target.

Keywords:
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Area of Science:

  • Immunology
  • Gerontology
  • Infectious Diseases

Background:

  • Sepsis is a critical global health issue, particularly impacting older adults.
  • Previous research implicated interferon regulatory factor 3 (IRF3) in sepsis pathogenesis in younger individuals.
  • The role of IRF3 in sepsis within the context of aging remained unexplored.

Purpose of the Study:

  • To investigate the contribution of IRF3 to sepsis pathogenesis in aged mice.
  • To determine if targeting IRF3 could offer protective effects against sepsis in older individuals.

Main Methods:

  • A cecal ligation and puncture (CLP) sepsis model was employed in aged wild-type (WT) and IRF3-knock-out (KO) mice.
  • Survival rates, disease scores, and hypothermia were assessed as sepsis indicators.
  • Serum cytokine levels and organ damage markers were quantified.

Main Results:

  • Aged WT mice exhibited high sepsis susceptibility (90% mortality), while aged IRF3-KO mice showed significant protection (20% mortality).
  • IRF3-KO mice displayed reduced disease severity and hypothermia post-CLP.
  • Lower levels of IL-6, IL-12/23p40, MCP-1, and creatinine kinase were observed in septic IRF3-KO mice.
  • Aged male mice were more susceptible than females, though females showed higher cytokine and CK levels.

Conclusions:

  • IRF3 plays a detrimental role in sepsis progression in aged mice.
  • These findings suggest IRF3 as a potential therapeutic target for sepsis in the elderly.
  • Biological sex significantly influences sepsis susceptibility and immune response in aged mice.