ABSTRACT
Corticosteroids effectively suppress airway inflammation, but there is considerable debate concerning the utility of these agents in the long-term treatment of patients with chronic obstructive pulmonary disease (COPD) [1,2]. The critiques to their use are: (1) the neutrophilic inflammation, which is characteristic in COPD [3-8], is generally resistant to corticosteroids; (2) corticosteroids prolong the survival of neutrophils by inhibiting apoptosis; and (3) corticosteroid therapy fails to suppress cytokines such as tumor necrosis factor (TNF)-a and interleukin (IL)-8, which are generally considered to be important mediators in neutrophil recruitment and are elevated in patients with COPD [9]. However, the observation that increased numbers of neutrophils are present during acute exacerbations of COPD and acute exacerbations do respond to oral corticosteroids might suggest that neutrophilic inflammation does not per se reflect unresponsiveness to oral or inhaled corticosteroids [10]. Recently, it has been suggested that the lack of efficacy of corticosteroids in attenuating airway inflammation could be due to a reduced corticosteroid sensitivity of macrophages [11]. Macrophages from subjects withCOPDare defective in histone deacetylase activity, which is an important
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mechanism in switching off proinflammatory genes in cells [12]. Any lack of efficacy of corticosteroids on macrophage activity in COPD could lead to reduced inhibition of neutrophil chemoattractants and increased survival, with perpetuation of pulmonary neutrophilic inflammation [11].
