[The effects of recombinant human tumor necrosis factor-Fc on pulmonary function in a rat model of chronic obstructive pulmonary disease].
OBJECTIVE
To investigate the influence of recombinant human tumor necrosis factor-Fc (rhTNFR: Fc) on pulmonary function in a rat model of chronic obstructive pulmonary disease (COPD).


METHODS
Forty-eight rats were randomly divided into a normal control group, a COPD group, a rhTNFR: Fc-intervention group and a sham intervention group. The COPD model was established by exposure to cigarette smoking daily for 80 days. The intervention group was treated with rhTNFR: Fc, and the sham intervention group injected with a preparation (normal saline 0.1 ml, manicol 0.8 ml, cane sugar 0.2 mg, Tris 0.024 mg) as control. The levels of tumor necrosis factor alpha (TNF-alpha) in serum and BALF were measured with ELISA. Lung tissue section stained by hematoxylin and eosin was observed to study the morphological alternations. Mean linear intercept (MLI) and mean alveolar numbers (MAN) were measured, and the lung function detected.


RESULTS
Compared with the normal control [(85.6 +/- 5.9)%, (47.2 +/- 7.3) ml/s], and the rhTNFR: Fc-intervention group [(77.7 +/- 2.7)%, (38.2 +/- 3.3) ml/s], FEV(0.3)/FVC and PEF were lower in the COPD rats [(65.1 +/- 8.4)%, (18.8 +/- 1.6) ml/s]. The levels of TNF-alpha in serum were higher in the COPD group [(118 +/- 34) ng/L] than in the normal control [(74 +/- 16) ng/L] and the rhTNFR: Fc-intervention group [(79 +/- 14) ng/L]. Significant differences were found between rhTNFR: Fc-intervention group and sham intervention group. The levels of TNF-alpha in BALF were higher in the COPD group [(155 +/- 28) ng/L] than in the normal control [(79 +/- 28) ng/L], but no significant differences were found between the levels in the COPD group and the sham intervention group. MLI in the COPD rats [(77 +/- 29) x 10(-6) m] was higher than that in the normal control[(44 +/- 7) x 10(-6) m] while MAN was decreased on the contrary, compared with the normal control and the rhTNFR: Fc-intervention group. Significant differences were found between MAN in the rhTNFR: Fc-intervention group and the sham intervention group. Negative correlations were demonstrated between the levels of TNF-alpha in serum and BALF and PEF and FEV(0.3)/FVC in the COPD group + sham intervention group.


CONCLUSIONS
TNF-alpha contributes to the pathogenesis of COPD and affects pulmonary function. rhTNFR:Fc may play a role in the improvement of pulmonary function in COPD.
Department of Respiratory Medicine, Xiangya Second Hospital of Central South University, Changsha 410011, China.
Cheng
C
Zhang
Ping
P
Chen
Shan
S
Cai
Jian-Bo
JB
Chen
Jie
J
Wu
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D000068800:Etanercept; D005541:Forced Expiratory Volume; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012906:Smoke; D014026:Nicotiana / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept