Is loaded breathing an inflammatory stimulus?

Curr Opin Crit Care. 2005 Feb;11(1):1-9. doi: 10.1097/00075198-200502000-00002.


Purpose of review: To summarize recent data indicating that loaded breathing generates an inflammatory response.

Recent findings: Loaded breathing initiates an inflammatory response consisting of elevation of plasma cytokines and recruitment and activation of lymphocyte subpopulations. These cytokines do not originate from monocytes but are instead produced within the diaphragm secondary to the increased muscle activation. Oxidative stress is a major stimulus for the cytokine induction secondary to loaded breathing. The production of cytokines within the diaphragm may mediate the diaphragm muscle fiber injury that occurs with strenuous contractions, or contribute to the expected repair process. These cytokines may also compromise diaphragmatic contractility or contribute to the development of muscle cachexia. They may also have systemic effects, mobilizing glucose from the liver and free fatty acids from the adipose tissue to the strenuously working respiratory muscles. At the same time, they stimulate the hypothalamic-pituitary-adrenal axis, leading to the production of adrenocorticotropic hormone and beta-endorphins. The adrenocorticotropic hormone response may represent an attempt of the organism to reduce the injury occurring in the respiratory muscles through the production of glucocorticoids and the induction of the acute-phase response proteins. The beta-endorphin response would decrease the activation of the respiratory muscles and change the pattern of breathing, which becomes more rapid and shallow, possibly in an attempt to reduce and/or prevent further injury to the respiratory muscles.

Summary: Loaded breathing is an immune challenge for the body, initiating an inflammatory response. Further studies are needed to elucidate the role of this response in the development of ventilatory failure.

Publication types

  • Review

MeSH terms

  • Airway Resistance / immunology*
  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Endorphins / metabolism
  • Humans
  • Hypothalamo-Hypophyseal System / immunology
  • Hypothalamo-Hypophyseal System / metabolism
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Inflammation / physiopathology*
  • Physical Endurance / immunology
  • Pituitary-Adrenal System / immunology
  • Pituitary-Adrenal System / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Respiratory Insufficiency / immunology
  • Respiratory Insufficiency / metabolism
  • Respiratory Insufficiency / physiopathology
  • Respiratory Mechanics / immunology*
  • Respiratory Muscles / metabolism
  • Respiratory Muscles / physiopathology


  • Cytokines
  • Endorphins
  • Reactive Oxygen Species