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Protecting the kidney in sepsis: resident macrophages to the rescue

Kevin D Burns1, Adrianna Douvris1

  • 1Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Kidney International
|February 23, 2023
PubMed

Insights

Kidney macrophages protect against sepsis-induced kidney injury. They express interleukin-1 receptor antagonist, blocking harmful interleukin-6 production, offering new therapeutic targets for kidney protection.

Area of Science:

  • Immunology
  • Nephrology
  • Sepsis Research

Background:

  • Kidney resident macrophages have varied roles in acute kidney injury.
  • The specific function of kidney macrophages during sepsis remains largely unknown.
  • Understanding these roles is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of kidney resident macrophages in sepsis-induced kidney injury.
  • To identify the mechanisms by which these macrophages influence kidney damage during sepsis.

Main Methods:

  • Utilized a mouse model of sepsis.
  • Analyzed the expression of key inflammatory mediators by kidney macrophages.
  • Investigated the interaction between macrophages and endothelial cells in the kidney.

Main Results:

  • Kidney resident F4/80hi macrophages were found to be protective against kidney injury in sepsis.
  • These macrophages express interleukin-1 receptor antagonist (IL-1RA).
  • IL-1RA selectively inhibited interleukin-6 (IL-6) production by endothelial cells, thereby reducing kidney injury.

Conclusions:

  • Kidney resident macrophages play a protective role in sepsis-induced kidney injury.
  • A novel autocrine loop involving IL-1RA and IL-6 blockade by endothelial cells was identified.
  • This discovery opens avenues for targeted therapies to prevent kidney damage during sepsis.

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