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DNA and actin bind and inhibit interleukin-8 function in cystic fibrosis sputa: in vitro effects of mucolytics

B Perks1, J K Shute

  • 1Department of Medical Specialties, Southampton General Hospital, Southampton, United Kingdom.

American Journal of Respiratory and Critical Care Medicine
|November 9, 2000
PubMed

Insights

Cystic fibrosis (CF) airway inflammation involves neutrophils and interleukin-8 (IL-8). Mucolytic treatments like DNase I and gelsolin reduce sputum viscosity but may increase free IL-8, potentially worsening inflammation.

Area of Science:

  • Pulmonary Medicine
  • Immunology
  • Biochemistry

Background:

  • Cystic Fibrosis (CF) is characterized by exaggerated neutrophil inflammation mediated by interleukin-8 (IL-8).
  • Neutrophil-released DNA and actin increase airway secretion viscoelasticity.
  • Mucolytics aim to improve airway clearance by reducing sputum viscoelasticity.

Purpose of the Study:

  • To investigate the interaction between airway polymers (DNA, actin) and IL-8.
  • To evaluate the impact of mucolytic agents (DNase I, gelsolin) on IL-8 availability and neutrophil chemotaxis.
  • To assess the potential inflammatory risks associated with current and future mucolytic therapies in CF.

Main Methods:

  • In vitro analysis of CF sputum viscosity.
  • Assessment of free IL-8 levels and neutrophil chemotactic activity in sputum supernatants.
  • Evaluation of DNA and actin binding to IL-8.

Main Results:

  • DNA and actin bind and mask IL-8, inhibiting its interaction with neutrophil receptors.
  • DNase I and gelsolin reduce sputum viscosity, increasing free IL-8 proportion.
  • This increase in free IL-8 correlates with enhanced IL-8-dependent neutrophil chemotaxis.

Conclusions:

  • An electrostatic interaction between airway polymers and IL-8 may naturally limit CF inflammation.
  • Cleavage of these polymers by mucolytics like DNase I or gelsolin can release IL-8.
  • This mechanism suggests a potential risk of increased inflammation with these mucolytic treatments in CF patients.

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