title: Patterns of cytokine release and evolution of remote organs from proximal femur fracture in COPD rats.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is at increased risk for developing osteoporosis (OP) with subsequent proximal femur fracture. The presence of COPD is suggested to be a strong risk factor for proximal femur fracture or hip fracture. However, what happen behind it is not clearly understood.
  
  
  OBJECTIVE
  To investigate the pattern of cytokine (TNF-a, IL-6, and IL-10) releases in pulmonary and hepatic in rats with COPD suffering from proximal femur fracture, and its possible adverse effect on pulmonary and hepatic.
  
  
  METHODS
  This paper has two parts. In the first part, we describe the procedure of COPD model in detail. In the second part, we study the influences of fracture on the COPD rats. 5 months WISTAR rats with 37 weeks cigarette smoking exposure (CS group) were dynamically determined for pulmonary function, inflammatory response in bronchoalveolar lavage fluid (BALF), histological changes in pulmonary in the first part. When the COPD model is proved to be successful, we begin the second part. COPD rats were euthanized at 2, 24, 48, 72, and 96h after proximal femur fracture (fracture group) or anaesthesia (control group). Cytokines (TNF-a, IL-6, and IL-10) and myeloperoxidase activity of pulmonary and hepatic (MPO) were measured with enzyme-liked immunosorbent assay technique. Permeability changes of the lung were assessed via bronchoalveolar lavage, and those of the liver via assessment of oedema formation. Tissues were further examined microscopically.
  
  
  RESULTS
  The current sidestream cigarette smoke induced rat COPD model has been proved an adequate animal model with several advantages as assessed by dynamically monitored lung mechanics and pathological changes for 37 weeks. In the second part, TNF-a, IL-6, and IL-10 levels of pulmonary tissue were significantly increased after proximal femur fracture compared to control rats. TNF-a, and IL-6 levels in pulmonary peaked at 2h, 24h in fracture group, whereas IL-10 level peaked at 24h and 96h. Pulmonary myeloperoxidase activity, permeability and histological score in fracture group were remarkably elevated, and peaked at 24h. In addition to TNF-a, all above parameters did not return to normal through our study. Hepatic in COPD rats showed notable increase of cytokines (TNF-a, IL-6, and IL-10), myeloperoxidase activity, histological score, and permeability in fracture group compared to control rats, and severity of these changes were much lower than in pulmonary. Apart from TNF-a, the peak of these parameters was at 24h after fracture. Changes of cytokines, MPO activity, permeability and histological score in pulmonary and hepatic in control rat were little changed.
  
  
  CONCLUSIONS
  COPD rats produced a remarkably increase of inflammatory response (TNF-a, IL-6, IL-10) in lung (liver) after proximal femur fracture, which lead to lung (liver) injury, as evidence by changes of MPO, permeability, and histological scores in local organs.
authors.affiliation: Department of Orthopedic, Beijing Army General Hospital, Dongcheng District, Nanmencang No. 5, Beijing, China. suntiansheng-@163.com
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Sun
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.forename: Shuqing
authors.initials: S
authors.lastname: Liu
authors.forename: Jianzheng
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015519:Bone Density; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000503:physiopathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009195:Peroxidase