Cellular effects of corticosteroids include a reduction in inflammatory cells and mediators, such as mast cells, eosinophils, T-cell cytokines, macrophage cytokines, and dendritic cell numbers. They also reduce endothelial cell number and leakage, goblet cell mucus secretion, and the production of cytokines from smooth-muscle cells. Numerous stud-ies have described the effects of ICS on noninvasive measures of airway inflammation, and readers are directed to current literature reviews for further information.
Expression of a smooth-muscle actin in fibroblasts in the early stages of differentiation has been shown to be inhibited by corticosteroid treatment. Constitutive expression of a smooth-muscle actin was low in myofibroblasts at an early stage of differentiation, intermediate in mildly differentiated lung fibroblasts, and complete in fully differentiated lung myofibroblastic cultures.
Fluticasone totally inhibited a smooth-muscle actin expression in early differentiated fibroblastic cultures, partially inhibited expression in mildly differentiated cultures, but was not inhibitive of expression in fully differentiated cells. Similarly, fluticasone inhibited tumor growth factory-induced a smooth-muscle actin expression in both early and mildly differentiated fibroblasts, but again was ineffective on totally differentiated lung myofibroblasts. These findings may help to explain why asthma is improved by early ICS, whereas advanced asthma is more resistant to these drugs. In children, it has been shown that when ICS were begun within 2 years of asthma onset, FEVX was significantly higher (p < 0.05) than if ICS were started later than 5 years after asthma onset. More info
ICS remain the cornerstone of treatment for the long-term control of asthma. Recent studies suggest that the antiinflammatory efficacy of ICS may be enhanced through the use of combination therapy with long-acting B-agonists (LABAs). Whether or not LABAs themselves possess clinically important effects on inflammatory mediators, however, remains to be determined. Although ICS are the “gold standard” of control therapy for asthma, there are still concerns about local and systemic side effects. This subject is discussed in the article by Irwin on side effects. Minimization of some of these problems may result in an ICS with an improved safety profile.