Abstract:

Objective To discuss the expression levels of interleukin-33 （IL-33）， interleukin-8 （IL-8）， and the major components of neutrophil extracellular traps （NETs）-myeloperoxidase （MPO） and citrullinated histone H3 （CitH3） in lung tissue of the patients with chronic obstructive pulmonary disease （COPD）， and to clarify the effects of IL-33， IL-8， and NETs on the occurrence and development of COPD. Methods Seventy-seven patients underwent lobectomy due to pulmonary nodules or lung tumors were selected as the subjects and divided into non-smoking control group （20 cases）， smoking control group （18 cases）， non-smoking COPD group （19 cases）， and smoking COPD group （20 cases）.The lung tissue samples from the subjects were collected.HE staining was used to observe the pathomorphology of lung tissue of the patients in various groups；immunohistochemisty staining was used to detect the expression levels of IL-33， IL-8， CitH3， and MPO proteins in lung tissue of the patients in various groups； Spearman correlation analysis was used to detect the relationship between expression levels of IL-33， IL-8， CitH3， and MPO proteins in lung tissue of the patients in COPD groups and their correlations with lung function index， mean linear intercept （MLI）， mean alveolar number （MAN）， and Bosken score. Results Compared with non-smoking control group， the airway Bosken score of the patients in smoking control group was significantly increased （P<0.001）； compared with non-smoking control and smoking control groups， the airway Bosken score and MLI of the patients in non-smoking COPD group were significantly increased （P<0.05）， while the MAN was significantly decreased （P<0.05）； compared with non-smoking control group， smoking control group， and non-smoking COPD group， the airway Bosken score of the patients in smoking COPD group was significantly increased （P<0.05）； compared with non-smoking control group and smoking control group， the MLI of the patients in smoking COPD group was significantly increased （P<0.05）， and the MAN was significantly decreased （P<0.05）. The immunohistochemisty staining results showed that compared with non-smoking control group， smoking control group， and non-smoking COPD group，the expression level of IL-33 in lung tissue of the patients in smoking COPD group was significantly increased （P<0.05）； compared with non-smoking control group and smoking control group，the expression levels of IL-8， CitH3， and MPO proteins in lung tissue of the patients in smoking COPD group were significantly increased （P<0.05）. Compared with non-smoking control group and smoking control group， the expression levels of IL-33， IL-8， CitH3， and MPO proteins in lung tissue of the patients in non-smoking COPD group were significantly increased （P<0.05）.The Spearman correlation analysis results showed that there was a negative correlation between the expression level of IL-33 protein and forced expiratory volume in first second/forced vital capacity （FEV1/FVC）， the forced expiratory volume in first second predicted FEV1 （FEV1%pred）， and MAN （r=－0.406， P<0.05； r=－0.493， P<0.01； r=－0.567， P<0.05） in lung tissue of the patients in COPD group， and there was a positive correlation with Bosken score and MLI （r=0.935， P<0.001； r=0.590， P<0.001）；the expression level of IL-8 protein in lung tissue of the patients in COPD group was negatively correlated with the FEV1/FVC， FEV1%pred， and MAN （r=－0.527， P<0.01； r=－0.497， P<0.01； r=－0.463， P<0.01）， and was positively correlated with the Bosken score and MLI （r=0.557， P<0.001； r=0.486， P<0.01）； the expression level of CitH3 protein in lung tissue of the patients in COPD group was negatively correlated with the FEV1/FVC， FEV1%pred， and MAN （r=－0.527， P<0.01； r=－0.640， P<0.001； r=－0.531， P<0.01）， and was positively correlated with the Bosken score and MLI （r=0.565， P<0.001； r=0.585， P<0.001）；the expression level of MPO protein in lung tissue of the patients in COPD group was positively correlated with the FEV1/FVC （r=－0.329， P<0.05）， and was positively correlated with the Bosken score （r=0.410， P<0.05）； the expression level of IL-8 protein was positively correlated with the expression levels of CitH3 and MPO proteins （r=0.390，P<0.05； r=0.349， P<0.05）； the expression level of IL-33 protein was positively correlated with the expression levels of IL-8， CitH3， and MPO proteins （r=0.602，P<0.001； r=0.616，P<0.001； r=0.387， P<0.05）. Conclusion The expression levels of IL-33， IL-8， and NETs in lung tissue of the COPD patients are increased， and they may be involved in the chronic inflammation of COPD and correlated with the severity of the disease.

Key words: Chronic obstructive pulmonary disease, Interleukin-33, Interleukin-8, Neutrophil extracellular traps, Smoking