Ventilatory muscle activation and inflammation: cytokines, reactive oxygen species, and nitric oxide

• Published in: Journal of applied physiology (1985) Vol. 102; no. 4; pp. 1687 - 1695
• Main Authors: Vassilakopoulos, Theodoros, Hussain, Sabah N. A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.04.2007; American Physiological Society
• Subjects: Animals; Biological and medical sciences; Cytokines; Cytokines - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Humans; Immune system; Inflammation - metabolism; Models, Biological; Muscle Contraction; Nitric oxide; Nitric Oxide - metabolism; Pulmonary Ventilation; Reactive Oxygen Species - metabolism; Respiratory diseases; Respiratory Muscles - physiopathology; Reactive oxygen species; Immune response; Respiratory disease; Cytokine; Inflammation; Striated muscle; immune challenge; Vertebrata; Mammalia; Nitric oxide; respiratory diseases; Respiration; control of breathing
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.01273.2006

1 Department of Critical Care and Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, Athens, Greece; and 2 Critical Care and Respiratory Divisions and Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada Strenuous diaphragmatic contractions that are induced by inspiratory resistive breathing initiate an inflammatory response that involves the elevation of pro- and anti-inflammatory cytokines within the diaphragm, which may then spill into the circulation. The production of reactive oxygen species within working respiratory muscles increases in response to these strenuous diaphragmatic contractions. At the same time, diaphragmatic nitric oxide (NO) production declines significantly, despite a time-dependent increase in NO synthase isoform protein expression. The increase in adhesion molecule expression and infiltration of granulocytes and macrophages that follows may contribute to the contraction-induced diaphragm injury. Enhanced generation of reactive oxygen species, oxidative stress augmentation, reduced NO production, and glycogen depletion are potential stimuli for the cytokine induction that is secondary to strenuous diaphragmatic contractions. This production of cytokines within the diaphragm may contribute to the diaphragmatic muscle fiber injury that occurs with strenuous contractions or to the expected repair process. TNF- is a cytokine that compromises diaphragmatic contractility and may contribute to muscle wasting. IL-6 is a cytokine that may have beneficial systemic effects by mobilizing glucose from the liver and free fatty acids from the adipose tissue and providing them to the strenuously working respiratory muscles. Thus cytokine upregulation within the working diaphragm may be adaptive and maladaptive. control of breathing; immune response; respiratory diseases; immune challenge Address for reprint requests and other correspondence: S. N. A. Hussain, Dept. of Medicine, McGill Univ., Montreal, PQ, Canada H3A 1A1 (e-mail: sabah.hussain{at}muhc.mcgill.ca )