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The biological effects of lung-derived mediators on the liver

Nicole A Rocca1, Melissa G Walker, Lynda A McCaig

  • 1Department of Physiology and Pharmacology and Lawson Health Research Institute, University of Western Ontario, London, Canada.

Experimental Lung Research
|July 27, 2011
PubMed

Insights

Lung-derived inflammatory mediators from acute lung injury significantly harm distant organs. Targeting these mediators may prevent multiorgan failure and improve survival in patients receiving mechanical ventilation.

Area of Science:

  • Pulmonary Medicine
  • Inflammation Research
  • Organ Crosstalk

Background:

  • Acute lung injury (ALI) has high mortality (30-40%) due to multiorgan failure.
  • Lung-protective mechanical ventilation (MV) is used, but outcomes remain poor.
  • The role of lung-derived mediators in peripheral organ inflammation is not fully understood.

Purpose of the Study:

  • To investigate the biological impact of lung-derived mediators on peripheral organs.
  • To determine if mediators from inflamed lungs cause inflammation in other organs.

Main Methods:

  • An isolated perfused mouse lung model was used to induce lipopolysaccharide (LPS)-mediated lung inflammation.
  • Protective mechanical ventilation (MV) was applied to collect lung perfusate.
  • Perfusate was intravenously injected into normal mice, and their livers were assessed using intravital video microscopy.

Main Results:

  • Perfusate from LPS-inflamed lungs had higher inflammatory mediator concentrations than controls.
  • Liver assessment showed reduced sinusoidal blood flow, increased white blood cells, and cell death in mice receiving perfusate from inflamed lungs.
  • No adverse effects were observed with pure perfusate or LPS mixed with perfusate, indicating lung mediators were responsible.

Conclusions:

  • Lung-derived mediators from ALI significantly impact peripheral organs, causing inflammation and damage.
  • These findings highlight the critical role of lung-derived factors in ALI-associated multiorgan failure.
  • Therapeutic strategies targeting these specific mediators could potentially reduce mortality in ALI patients.

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