title: Molecular mechanisms of inflammation during exacerbations of chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Exacerbations of chronic obstructive pulmonary disease (COPD) are characterised by an inflammatory and systemic response that persists for some time after their clinical resolution. The mechanisms of this inflammatory process are not well known.
  
  
  OBJECTIVE
  To explore the inflammatory changes and possible mechanisms during COPD exacerbation.
  
  
  METHODS
  We determined the inflammatory cell concentrations in blood and sputum, nitric oxide in exhaled air (FeNO), C-reactive protein (CRP) in plasma, cytokines (IL-6, 8, 1β, 10, 12, TNF-α) and SLPI (leukocyte protease inhibitor) and total antioxidant status (TAS) in blood and sputum, the activity of nuclear kappa B factor (NF-κ B) and of the histone deacetylase enzyme (HDAC) in 17 patients during COPD exacerbation and in stable phase, as well as in 17 smoker and 11 non-smoker controls.
  
  
  RESULTS
  COPD exacerbations are characterised by high levels of FeNO (p<0.05), plasma CRP (p<0.001) and IL-8, IL-1B, IL-10 in sputum (p<0.05) greater activation of NF-κ appaB in sputum macrophages compared with stable COPD and controls. During the stable phase, there continue to be high levels of oxidative stress, SLPI, IL-8, IL-6 and TNF-alfa, with no observed changes in either HDAC activity or in the amount of neutrophils in sputum, despite presenting a significant improvement (p<0.05) in lung function.
  
  
  CONCLUSIONS
  Changes were observed in different pulmonary and systemic inflammatory markers during COPD exacerbation, which did not completely resolve during stable phase. However, current treatment does not allow for HDAC activity to be modified, which limits its anti-inflammatory effects.
authors: Servicio de Neumología, Hospital Universitario Son Dureta, Palma de Mallorca, Spain.
authors: Ana L
authors: AL
authors: Kersul
authors: Amanda
authors: A
authors: Iglesias
authors: Ángel
authors: Á
authors: Ríos
authors: Aina
authors: A
authors: Noguera
authors: Aina
authors: A
authors: Forteza
authors: Enrique
authors: E
authors: Serra
authors: Alvar
authors: A
authors: Agustí
authors: Borja G
authors: BG
authors: Cosío
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000032:analysis; D015415:Biomarkers; D001773:Blood Cells / Q000473:pathology; D001944:Breath Tests; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000032:analysis; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000503:physiopathology; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000097:blood; D012907:Smoking / Q000378:metabolism; D013147:Spirometry; D013183:Sputum / Q000737:chemistry / Q000166:cytology; D014158:Transcription, Genetic
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D016328:NF-kappa B; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D009569:Nitric Oxide; D002097:C-Reactive Protein; D006655:Histone Deacetylases