Pharmacological strategies to regain steroid sensitivity in severe asthma and COPD.

Pharmacological strategies to regain steroid sensitivity in severe asthma and COPD. Curr Opin Pharmacol. 2019 May 08;46:73-81 Authors: Mei D, Tan WSD, Wong WSF Abstract Corticosteroid is the most widely used anti-inflammatory agent for asthma and chronic obstructive pulmonary disease (COPD). However, most of the severe asthmatics and COPD patients show poor response to the anti-inflammatory benefits of corticosteroids. Corticosteroid resistance is a major therapeutic challenge to the treatment of severe asthma and COPD. Cellular and molecular mechanisms underlying steroid insensitivity in severe asthma and COPD are still not fully understood. This review aims to recapitulate recent discoveries of potential contributing mechanisms of steroid resistance, and to appraise new therapeutic strategies shown to restore steroid sensitivity in experimental models of severe asthma and COPD, and in human clinical trials. It has been revealed that pro-inflammatory cytokines such as IFN-γ, TNF-α, TGF-β, IL-17A, IL-27, IL-33 and thymic stromal lymphopoietin (TSLP) may contribute to steroid resistance in severe asthma and COPD. These cytokines together with allergens, pathogens, and cigarette smoke can modulate multiple signaling pathways including PI3Kδ/Akt/mTOR, JAK1/2-STAT1/5, p38MAPK/JNK, Nrf2/HDAC2/c-Jun, heightened glucocorticoid receptor (GR)β/GRα ratio, and casein kinase 1 (CK1δ/ε)/cofilin 1, to induce steroid insensitivity. More rec...
Source: Current Opinion in Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Opin Pharmacol Source Type: research