Changes of leukotriene B4 in chronic obstructive pulmonary disease and effects of theophylline on leukotriene B4

Yanling DING; Wanzhen YAO

ABSTRACT

Objective:

To investigate the changes of leukotriene B4 (LTB4) in both the airways and the blood circulation in an animal model of chronic obstructive pulmonary disease (COPD) and the effects of theophylline on LTB4.

Methods:

Thirty-two male Wistar rats were divided into four groups by random number meter Group A (normal controls), group B (COPD), group C (smoking+low dose theophylline), and group D (smoking+high dose theophylline ),with 8 rats in each group. Pulmonary functions of the rats were assessed, and pathological changes of airways were scored. Cell counts and cell differentiation in bronchoalveolar lavage fluid (BALF) were also performed. Concentrations of IL-8 and LTB4 in BALF, plasma and lung tissue were measured by enzyme-linked immunosorbent assay (ELISA) and enzyme immunoassay (EIA).

Results:

LTB4 concentrations in BALF of COPD rats increased significantly as compared with the normal controls, and positively correlated with the percentage of neutrophil and IL-8 in BALF (r=0.794,0.863 ; P=0.007,0.012), and negatively correlated with peak expiratory flow (PEF) (r=-0.718, P=0.028). Positive correlations were also found between levels of LTB4 in BALF and the scores of inflammatory cell infiltration of COPD rats (r=0.836, P=0.036). Treatment with theophylline decreased the percentage of neutrophil and the concentrations of LTB4 in BALF of the COPD rats, attenuated the pathological changes of small airways, such as airway occlusion, goblet-cell metaplasia, inflammatory cell infiltration, and fibrosis and smooth muscle proliferation. The effect was more significant on goblet-cell metaplasia and inflammatory cell infiltration in the high dose group. However theophylline had little effect on PEF.

Conclusion:

Our results suggest that LTB4 is involved in airway inflammation in COPD. Theophylline is effective in decreasing the levels of LTB4 in BALF of COPD rats, reducing the percentage of neutrophil, and attenuating pathological changes of small airways.