title: Bilirubin treatment suppresses pulmonary inflammation in a rat model of smoke-induced emphysema.
abstract: BACKGROUND
  Cigarette smoking is a significant risk factor for emphysema, which is characterized by airway inflammation and oxidative damage.
  
  
  OBJECTIVE
  To assess the capacity of bilirubin to protect against smoke-induced emphysema.
  
  
  METHODS
  Smoking status and bilirubin levels were recorded in 58 patients with chronic obstructive pulmonary diseases (COPD) and 71 non-COPD participants. The impact of smoking on serum bilirubin levels and exogenous bilirubin (20 mg/kg/day) on pulmonary injury was assessed in a rat model of smoking-induced emphysema. At sacrifice lung histology, airway leukocyte accumulation and cytokine and chemokine levels in serum, bronchoalveolar lavage fluid (BALF) and lung were analyzed. Oxidative lipid damage and anti-oxidative components was assessed by measuring malondialdehyde, superoxide dismutase (SOD) activity and glutathione.
  
  
  RESULTS
  Total serum bilirubin levels were lower in smokers with or without COPD than non-smoking patients without COPD (P < 0.05). Indirect serum bilirubin levels were lower in COPD patients than patients without COPD (P < 0.05). In rats, cigarette smoke reduced serum total and indirect bilirubin levels. Administration of bilirubin reduced mean linear intercept and mean alveoli area, increased mean alveoli number, reduced macrophage, neutrophil and TNF-α content of BALF, and increased BALF and serum IL-10 level, but lowered local and systemic CCL2, CXCL2, CXCL8 and IL-17 levels. Bilirubin suppressed the smoke-induced systemic and regional oxidative lipid damage associated with increased SOD activity.
  
  
  CONCLUSIONS
  Bilirubin attenuated smoking-induced pulmonary injury by suppressing inflammatory cell recruitment and pro-inflammatory cytokine secretion, increasing anti-inflammatory cytokine levels, and anti-oxidant SOD activity in a rat model of smoke-induced emphysema.
authors.affiliation: Department of Pediatrics, Shanxi Medical University, Taiyuan 030001, China; Department of Respiratory Medicine, Shanxi Medical University Second Hospital, Taiyuan 030001, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Respiratory Medicine, Shanxi Medical University Second Hospital, Taiyuan 030001, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Teaching and Research Office of Microbiology & Immunology, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Fan
authors.affiliation: Department of Respiratory Medicine, Shanxi Medical University Second Hospital, Taiyuan 030001, China. Electronic address: ljqhx@sina.com.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001663:Bilirubin / Q000378:metabolism / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005978:Glutathione / Q000819:agonists / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000037:antagonists & inhibitors / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011014:Pneumonia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011656:Pulmonary Emphysema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012906:Smoke / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D012906:Smoke; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione; D001663:Bilirubin
keywords: Bilirubin; Chemokines; Cigarette smoke; Cytokines; Emphysema; Oxidative stress