title: Inflammatory cytokine response to exercise in alpha-1-antitrypsin deficient COPD patients 'on' or 'off' augmentation therapy.
abstract: BACKGROUND
  There is still limited information on systemic inflammation in alpha-1-antitrypsin-deficient (AATD) COPD patients and what effect alpha-1-antitrypsin augmentation therapy and/or exercise might have on circulating inflammatory cytokines. We hypothesized that AATD COPD patients on augmentation therapy (AATD + AUG) would have lower circulating and skeletal muscle inflammatory cytokines compared to AATD COPD patients not receiving augmentation therapy (AATD-AUG) and/or the typical non-AATD (COPD) patient. We also hypothesized that cytokine response to exercise would be lower in AATD + AUG compared to AATD-AUG or COPD subjects.
  
  
  METHODS
  Arterial and femoral venous concentration and skeletal muscle expression of TNFα, IL-6, IL-1β and CRP were measured at rest, during and up to 4-hours after 50% maximal 1-hour knee extensor exercise in all COPD patient groups, including 2 additional groups (i.e. AATD with normal lung function, and healthy age-/activity-matched controls).
  
  
  RESULTS
  Circulating CRP was higher in AATD + AUG (4.7 ± 1.6 mg/dL) and AATD-AUG (3.3 ± 1.2 mg/dL) compared to healthy controls (1.5 ± 0.3 mg/dL, p < 0.05), but lower in AATD compared to non-AATD-COPD patients (6.1 ± 2.6 mg/dL, p < 0.05). TNFα, IL-6 and IL-1β were significantly increased by 1.7-, 1.7-, and 4.7-fold, respectively, in non-AATD COPD compared to AATD COPD (p < 0.05), and 1.3-, 1.7-, and 2.2-fold, respectively, compared to healthy subjects (p < 0.05). Skeletal muscle TNFα was on average 3-4 fold greater in AATD-AUG compared to the other groups (p < 0.05). Exercise showed no effect on these cytokines in any of our patient groups.
  
  
  CONCLUSIONS
  These data show that AATD COPD patients do not experience the same chronic systemic inflammation and exhibit reduced inflammation compared to non-AATD COPD patients. Augmentation therapy may help to improve muscle efflux of TNFα and reduce muscle TNFα concentration, but showed no effect on IL-6, IL-1β or CRP.
authors: Center for Cardiovascular and Respiratory Sciences, Division of Exercise Physiology, One Medical Center Dr, West Virginia University School of Medicine, Morgantown, WV 26506-9105, USA. molfert@hsc.wvu.edu.
authors: I Mark
authors: IM
authors: Olfert
authors: Moh H
authors: MH
authors: Malek
authors: Tomas M L
authors: TM
authors: Eagan
authors: Harrieth
authors: H
authors: Wagner
authors: Peter D
authors: PD
authors: Wagner
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D004357:Drug Synergism; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D012016:Reference Values; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein