Role of IL6 transsignaling during acute inflammation. (A) Acute inflammation stimulates tissue-resident mononuclear cells to secrete the proinflammatory cytokines TNFα, IL6, and IL1β, which in turn induce CXC-chemokines like KC secretion from endothelial cells. (B) Endothelial cells do not express membrane-bound IL6R and are therefore not responsive toward IL6 itself. Infiltrating neutrophils shed their IL6R upon apoptosis and the IL6/sIL6R complex stimulates endothelial cells to produce the CC-chemokine MCP1. MCP1 subsequently attracts mononuclear cells to the site of inflammation. (C) The replacement of neutrophils by mononuclear cells is an important intermediate step in the resolution of inflammation, which is controlled by the presence of sIL6R.