TY - JOUR T1 - JAK inhibitors overcome corticosteroid insensitivity in COPD JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p3835 AU - Patricia Macedo AU - Iain Kilty AU - Peter Barnes AU - Louise Donnelly Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p3835.abstract N2 - 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<0.05) from PBMC from NS and COPD patients. PF13 significantly suppressed all 3 CXCR3 chemokines in PBMC from COPD patients, CXCL9 and CXCL10 (p<0.001) from PBMC from NS and CXCL10 release from MDM from COPD patients (p=0.01) (Table 1). However, there were no differences in the response to JAK inhibition between subject groups.View this table:Table 1. Inhibition (%) of CXCR3 chemokine release by JAK inhibitors PF95 and PF13JAK inhibitors PF95 and PF13 significantly suppress steroid-insensitive CXCR3 chemokines in COPD cells and may have benefit as a novel anti-inflammatory treatment. ER -