Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1alpha, 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), and of pro-inflammatory cytokines, macrophage inflammatory protein-1alpha (MIP-1alpha), interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF), from blood monocytes and alveolar macrophages of mild asthmatic subjects in a double-blind, cross-over, placebo-controlled study. Budesonide reduced bronchial hyperresponsiveness and improved baseline FEV1. Alveolar macrophages were obtained by bronchoalveolar lavage performed at the end of each treatment phase. IL-10 from blood monocytes was not altered, but both IL-10 mRNA and protein expression from alveolar macrophages stimulated by lipopolysaccharide and IL-1beta were increased after corticosteroid therapy. By contrast, alveolar macrophages released significantly less MIP-1alpha, IFN-gamma, and GM-CSF after steroid treatment. In comparison to alveolar macrophages from normal nonasthmatic volunteers, those from asthmatic patients released more MIP-1alpha, IFN-gamma, and GM-CSF but lower amounts of IL-10 particularly at baseline and after IL-1beta stimulation. The ability of steroids to inhibit pro-inflammatory cytokines but to enhance the anti-inflammatory cytokine such as IL-10 may contribute to their beneficial actions in asthma. Asthma is characterized by alveolar macrophages exhibiting both an enhanced capacity to release pro-inflammatory cytokines and a reduced capacity to produce IL-10.
John
M
M
National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom.
Lim
S
S
Seybold
J
J
Jose
P
P
Robichaud
A
A
O'Connor
B
B
Barnes
P J
PJ
Chung
K F
KF
D000280:Administration, Inhalation; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D019819:Budesonide / Q000627:therapeutic use*; D016022:Case-Control Studies; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism*; D016753:Interleukin-10 / Q000032:analysis / Q000378:metabolism*; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism*; D008297:Male
D000893:Anti-Inflammatory Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D016753:Interleukin-10; D019819:Budesonide; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor