JAK inhibitors overcome corticosteroid insensitivity in COPD

Corticosteroid-insensitive CXCR3 chemokines (CXCL9, -10 and -11) are thought to drive the CD8 + inflammatory infiltrate in chronic obstructive pulmonary disease (COPD). These chemokines are elevated in COPD airways. This study investigated whether JAK inhibitors, PF95 and PF13, suppress CXCR3 chemokine release from macrophage lineage cells. Peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM) were isolated from non-smokers (NS), smokers (S) and COPD patients. Cells were pre-treated with either JAK inhibitor or dexamethasone (DEX) prior to stimulation with IFNγ. Cell media was harvested at 24h and chemokine release measured by ELISA. Compared to DEX, compound PF 95 significantly suppressed CXCL9, CXCL10 and CXCL11 (p JAK inhibitors PF95 and PF13 significantly suppress steroid-insensitive CXCR3 chemokines in COPD cells and may have benefit as a novel anti-inflammatory treatment.