Given that intrinsic CFTR dysregulation is now known to affect effector function directly in certain immune cells, including monocytes, and considering also the inflammatory mediators present in human CF circulation, which includes heightened levels of circulating lipopolysaccharide (LPS), C-reactive protein (CRP), and calprotectin (s100A8/s100A9) (31–33), we questioned the extent to which the observed hyperactivation of circulating monocytes is due to intrinsic or extrinsic factors in CF. The gene discussed is CFTR; the disease is cystic fibrosis.