INHALED CORTICOSTEROIDS INCREASE INTERLEUKIN-10 BUT REDUCE MACROPHAGEINFLAMMATORY PROTEIN-1-ALPHA, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, AND INTERFERON-GAMMA RELEASE FROM ALVEOLAR MACROPHAGES IN ASTHMA

We determined the effect of inhaled corticosteroid, budesonide, on the release of the anti-inflammatory cytokine, interleukin-10 (IL-10), an d of pro-inflammatory cytokines, macrophage inflammatory protein-1 alp ha (MIP-1 alpha), interferon-gamma (IFN-gamma), and granulocyte-macrop hage colony-stimulating factor (GM-CSF), from blood monocytes and alve olar macrophages of mild asthmatic subjects in a double-blind, cross-o ver, placebo-controlled study. Budesonide reduced bronchial hyperrespo nsiveness and improved baseline FEV1. Alveolar macrophages were obtain ed by bronchoalveolar lavage performed at the end of each treatment ph ase. IL-10 from blood monocytes was not altered, but both IL-10 mRNA a nd protein expression from alveolar macrophages stimulated by lipopoly saccharide and IL-1 beta were increased after corticosteroid therapy. By contrast, alveolar macrophages released significantly less MIP-1 al pha, IFN-gamma, and GM-CSF after steroid treatment. In comparison to a lveolar macrophages from normal nonasthmatic volunteers, those from as thmatic patients released more MIP-1 alpha, IFN-gamma, and GM-CSF but lower amounts of IL-10 particularly at baseline and after IL-1 beta st imulation. The ability of steroids to inhibit pro-inflammatory cytokin es but to enhance the anti-inflammatory cytokine such as IL-10 may con tribute to their beneficial actions in asthma. Asthma is characterized by alveolar macrophages exhibiting both an enhanced capacity to relea se pro-inflammatory cytokines and a reduced capacity to produce IL-10.