Structural Changes in Airway Diseases: Immunosuppressors

Structural Changes in Airway Diseases: ImmunosuppressorsMethotrexate is a folic acid antagonist that inhibits thymidine synthesis and thereby interferes with DNA synthesis. There is no consensus on the use of methotrexate in asthma, and nothing is known about its effects on remodeling. Azathioprine has no proven benefit in asthma. Cyclosporin A has inhibitory effects on mast cells, monocytes, neutrophils, basophils, and T-cells, and might have some benefit in severe corticosteroid-dependent asthma but no effect on remodeling has been described in hu-mans. However, in a cat model of asthma, cyclo-sporine A decreased inflammation and remodeling processes such as ASM hypertrophia and goblet-cell and submucosal gland hyperplasia. IV Igs have antiinflammatory properties as well; they may decrease the use of corticosteroids and reduce respiratory symptoms. Potential antiremodeling effects have not been assessed. add comment

The main target of new drugs for the prevention and treatment of asthma or COPD is the inflammatory process. Some agents, such as the CpG oligonucleotides or bacille Calmette-Gu^rin vaccine, are thought to be able to switch immune responses from a Th2 to a T-helper type 1 (Th1) profile. Anti-IL-5 antibodies target eosinophil-mediated inflammation. Rapamycin, a macrolide analog, has immunosuppressive effects and could influence inflammation and remodeling in experimental asthma mouse models. Selective phosphodiesterase inhibitors, through the breakdown of intracellular cyclic adenosine monophosphate, have bronchodilatory, antiinflammatory, and potential antiremodeling properties. Anticytokines: Soluble recombinant human IL-4 receptor has been used in humans and seems to have the same effectiveness on clinical outcomes as ICS. Unfortunately, no observations to date in either humans or animals have addressed an antiremodeling effect. In animal models of asthma, IL-4 receptor antagonists inhibit airway inflammation and AHR.

This entry was posted in Pulmonary Function and tagged airway inflammation, airway remodeling, antiasthmatic therapy, asthma, COPD, corticosteroids, cystic fibrosis.