Abstract
Lung fibroblasts are involved in airway inflammation and remodelling in COPD. We report an investigation of the effects of combining a p38 MAPK inhibitor with a corticosteroid on cytokine production by a human lung fibroblast cell line and primary fibroblasts obtained from human lung tissue. Our main interest was to determine whether additive or synergistic anti-inflammatory effects would be observed. We observed inhibition of IL-6 and CXCL8 secretion from both lung fibroblast models by dexamethasone (maximal inhibition 40-90%) and the p38 MAPK inhibitor BIRB (maximal inhibition 30-60%), used alone and evidence of increased anti-inflammatory effects when used in combination. This combination effect was more apparent for TNF-a stimulated cytokine production (maximal inhibition increased by 10-20%). Interaction ratio analysis showed this enhanced effect to be additive rather than synergistic interaction. Similar results were obtained using both fibroblast cell culture models. Combining a p38 MAPK to corticosteroids may help reduce fibroblast mediated inflammation in COPD.