The impacts of anti-inflammatory phosphodiesterase inhibitors on a murine model of chronic pulmonary inflammation

Abstract

Chronic obstructive pulmonary disease (COPD) often tends to respond poorly to glucocorticoid (GC) therapy. Reduced Histone deacetylase-2 (HDAC-2) activity is an important mechanism behind this GC insensitivity. In this study, we investigated the effects of three phosphodiesterase inhibitors (PDEIs), with anti-inflammatory propensity, on cigarette smoke (CS) induced pulmonary inflammation and HDAC-2 activity. Male C57BL/6 mice were exposed to cigarette smoke (CS) over the course of 30 weeks. Administration of the PDEIs commenced from the 29th week and followed a schedule of once daily treatments, 5 days a week, for 2 weeks. Roflumilast (ROF) was administered intragastrically (5 mg•kg-1), while pentoxifylline (PTX) (10 mg•kg-1) and theophylline (THEO) (10 mg•kg-1) were administered intraperitoneally, either alone or in combination with a GC (triamcinolone acetonide or TRI, 5 mg•kg-1, i.m., single injection). Lung morphometry, as well as the activity of HDAC-2, pro-inflammatory cytokines and reactive oxygen species (ROS) were assessed at the end of the 30 week course. CS exposure was associated with a reduction in HDAC-2 activity and the up-regulation of ROS expression. PTX, ROF and THEO administration led to the partial restoration of HDAC-2 activity, however combining TRI to any of these PDEIs did not synergistically augment this effect. The restoration of HDAC-2 activity was favorably associated with the reduction of ROS expression.Inactivation of HDAC-2 due to long-term CS exposure is closely related to exaggerated oxidative stress, and this reduced HDAC-2 activity could partially be restored through the use of PDEIs. This finding provides a potential novel approach for further clinical research.

Effects of combination treatment with theophylline sustained release tablets and thymalfasin on pulmonary function, immunity, and inflammation in elderly patients with chronic obstructive pulmonary disease and respiratory failure

“…The dual effect of continuous airway inflammation and decreased blood flow is continuous decreases in lung function leading to abnormal blood gas and decreased oxygenation, which aggravates the condition of the patient [8,9]. As a result of the continuous increase in immunology-related clinical research, it has been shown that immunomodulatory dysfunction contributes to the occurrence and progression of COPD with respiratory failure, and that regulation of immune function improves the condition of the patient [10]. The traditional clinical treatment of COPD with respiratory failure is based on conventional methods such as anti-inflammatory, antiinfective, and expectorant treatments to ameliorate the clinical symptoms by alleviating the inflammatory response.…”

Evaluation of the Effect of the “General Practitioner-Specialist” Combination in the Community Management of Chronic Obstructive Pulmonary Disease

“…Patients with chronic obstructive pulmonary disease not only have respiratory symptoms, but also involve the cardiovascular system [3], may also experience venous thromboembolism [4], and may also develop anxiety and depression. Therefore, we should pay more attention to the prevention and treatment of chronic obstructive pulmonary disease [5][6]. However, literature review studies have found that chronic obstructive pulmonary disease (COPD) has not been included in the national basic public health service projects [7], lacking policy support and community management guidelines for COPD.…”