Infiltration Of Pro-inflammatory Cells Research Articles

Doxycycline reduces cigarette smoke‐extract induced IL‐8 production in human moncyte and macrophage cells

Exposure to cigarette smoke eventually leads to the development of several serious chronic inflammatory lung diseases such as chronic bronchitis, COPD and emphysema. A common characteristic of these diseases is the infiltration of pro-inflammatory cells, such as monocytes and macrophages, in to lung tissues along with the production of pro-inflammatory molecules such as IL-8, MCP-1 and LTB4. The presence of these cells and molecules potentiate chronic inflammation and tissue damage in the lung. Doxycycline (DOX) and other antibiotics also exhibit anti-inflammatory properties and are used to treat chronic inflammation in a variety of lung diseases and rheumatoid arthritis. Human U937 monocytes and PMA-induced macrophages were grown in cell culture and exposed to varied doses (0.1 – 10%) of an aqueous cigarette smoke extract (CSE) and DOX (5-30 μg/ml). IL-8 production was measured in cell supernatants by ELISA. Unstimulated monocytes produced 105 pg/ml IL-8 (SD 8.9), whereas stimulation of these cells with 0.5% CSE produced 477 pg/ml IL-8 (SD 55.6). The addition of 30 μg/ml DOX decreased CSE-induced IL-8 to 21.1 pg/ml (SD 2.56). Unstimulated macrophages produced 89,030 pg/ml IL-8 (SD 810) and treatment with 0.5% CSE increased release to 135,660 pg/ml IL-8 (SD 25235). Addition of 30 μg/ml DOX markedly decreased IL-8 to 23,010 pg/ml (SD 2409). For both cell types, DOX treatment reduced CSE-stimulated IL-8 in a dose dependent manner. These results demonstrate that DOX treatment may provide an important anti-inflammatory therapy for smoke-induced lung damage. Research funded by FAMRI

Could isoenzyme-selective phosphodiesterase inhibitors render bronchodilator therapy redundant in the treatment of bronchial asthma?

Bronchial asthma is predominantly a disease of industrialized countries. Recently compiled statistics indicate that greater than 5% of the population suffers from asthma and that, unlike other common treatable conditions [ 11, the prevalence and severity of asthma are increasing [2] as is the number of reported cases of fatal asthma [3,4]. These are particularly alarming statistics given the marked increase in the prescribing of various anti-asthma therapies [5,6]. At least two explanations can be advanced to explain why currently available drugs fail to control asthma adequately: (1) they may be inactive or provide an inappropriate therapy, or (2) while efficacious, they are not being used optimally. It is the view of the author that in many cases the drugs prescribed while providing symptomatic relief are essentially inactive at controlling the progression of the disease. This may be due to the more recent realization that bronchial asthma is a chronic inflammatory disorder [7,8] rather than an intrinsic or acquired abnormality of airways smooth muscle function. Indeed, widespread submucosal inflammation, characterized by the infiltration of proinflammatory cells in particular eosinophils and Tlymphocytes together with epithelial sloughing, has been reported not only in individuals who have died from asthma [9] but in patients with only mild symptoms of the disease [lo, 111. Furthermore, the chronicity of the inflammation in asthma may lead eventually to a state of irreversible airways obstruction brought about by structural changes in