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  • Title: Dexamethasone and p38 MAPK inhibition of cytokine production from human lung fibroblasts.
    Author: Higham A, Singh D.
    Journal: Fundam Clin Pharmacol; 2021 Aug; 35(4):714-724. PubMed ID: 33145838.
    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.
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