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Morphine induced exacerbation of sepsis is mediated by tempering endotoxin tolerance through modulation of miR-146a

Santanu Banerjee1, Jingjing Meng, Subhas Das

  • 1Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.

Scientific Reports
|June 13, 2013
PubMed

Insights

Chronic morphine use disrupts endotoxin tolerance, causing persistent inflammation and septic shock. MicroRNA-146a (miR-146a) acts as a key regulator, with its overexpression preventing morphine-induced hyper-inflammation.

Area of Science:

  • Immunology
  • Pharmacology
  • Molecular Biology

Background:

  • Endotoxin tolerance normally prevents excessive inflammation during infections.
  • Chronic morphine use can interfere with this protective mechanism.

Purpose of the Study:

  • To investigate how chronic morphine treatment affects endotoxin tolerance.
  • To identify the role of specific microRNAs (miRNAs) in morphine-induced hyper-inflammation.

Main Methods:

  • Assessed endotoxin tolerance in a model of chronic morphine administration.
  • Quantified microRNA-146a (miR-146a) and microRNA-155 (miR-155) levels in macrophages.
  • Manipulated miR-146a and miR-155 levels to determine their functional impact.

Main Results:

  • Chronic morphine treatment impaired endotoxin tolerance, leading to persistent inflammation, septicemia, and septic shock.
  • Morphine down-regulated LPS-induced miR-146a and miR-155 in macrophages.
  • Overexpression of miR-146a, but not miR-155, reversed morphine-induced hyper-inflammation.
  • Inhibition of miR-146a exacerbated morphine-mediated inflammation.

Conclusions:

  • miR-146a functions as a critical molecular switch in controlling hyper-inflammation associated with morphine use.
  • Findings have implications for understanding risks in clinical and recreational morphine users.

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