IL-6 trans-signaling in the resolution of inflammation. The inflammatory response involves influx of polymorphonuclear leukocytes (PMNs or neutrophils). Phagocytosis of microbes and cell activation ultimately lead to PMN apoptosis (a-PMN), during which ADAM17 is activated to cleave IL-6R from the cell surface (shedding). IL-6 and soluble IL-6R derived from neutrophils signal recruitment of mononuclear phagocytes by IL-6 trans-signaling, possibly through endothelial cells. Phagocytosis of apoptotic neutrophils by mononuclear phagocytes, typically macrophages (Mφ), is a key step in the resolution of acute inflammation.