The nature of the inflammatory response is different from asthma and is determined by the activation of macrophages, epithelial cells of the respiratory tract, which in turn secrete one number of chemokines and lipid mediators entered Ing recruitment of neutrophils and T lymphocytes CD8t. The secretion of a variety of proteases of neutrophils and macrophages Dipeptidyl peptidase-4, contribute increased Ht mucus and atomizer tion of alveolar These pathological Ver Changes cause symptom my cough, mucus secreted, breathing problems and emphysema. Most of the cell types involved in the disease process PDE4 explicit. D PDE4A expression in peripheral blood neutrophils and CD8T cells in patients with mild COPD ver Changed. However, the expression of PDE4A4 and total cAMP-PDE activity T significantly in macrophages from bronchoalveol Ren lavage of patients cleaned with mild to moderate compared to healthy patients or smokers COPD n ‘erh ht Currently do not have COPD.
Of the 12 analyzed PDE4 variants, PDE4A4 activity was only t Erh Ht and suggested that local events / processes specifically upregulated in the lungs of COPD patients variant. There remains, however, Luteolin the functional consequence of this Change in the light of the results shows that the inhibition of PDE4 has an m Strength influence of tumor necrosis factor suppression of the production of human monocyte derived macrophages in culture can be determined, and the contribution of PDE3 PDE7 and regulatory function in this cell type can not be ignored. There are a limited number of in vivo animal models of COPD. However, the recruitment of neutrophils in the respiratory tract can be induced easily by using the component of the bacterial cell wall, endotoxin, though it is generally recognized that to model this stimulus by recruitment of neutrophils in the airways.
The recruitment of these cells in the airways of wild-type M was usen By about 50% in PDE4B and PDE4D-deficient M Inhibited nozzles, and h Heres Ma of inhibition was were wildtype M observed nozzles treated with rolipram. Again raised the r PDE4 isoforms complement Ren in the regulation of neutrophil recruitment into the airways. Similarly, cigarette neutrophil recruitment were induced in the airways release of chemokines and Ver changes Ged in emphysema Fights PDE4 inhibitors. Together, these studies demonstrate the usefulness of PDE4 inhibition in cell types involved in this disease. A number of clinical phase III studies, the potential utility of PDE4 inhibitors in the treatment of COPD.
The three studies reported small but significant improvements over placebo spirometry, the Lebensqualit t and reducing the number of exacerbations in the group of patients compared with COPD. The mechanism of improvement of spirometry is unlikely to be due to the relaxation of bronchial smooth muscle, because this class of drug is a low bronchodilator activity t. It is possible to change that this improvement is due to anti-inflammatory medication, even if no biomarkers of inflammation in these studies was measured. However, several studies have tried to determine whether PDE4 inhibitors are anti-inflammatory COPD.