Local and systemic effects of interleukin‐6 (IL‐6) in inflammation and cancer
2022
Rose‐John, Stefan
Interleukin‐6 (IL‐6) is an inflammatory cytokine, the level of which is highly elevated in most, if not all, inflammatory states. IL‐6 triggers cell type‐specific responses and acts on target cells via a specific interleukin‐6 receptor (IL‐6R), which, together with IL‐6, binds to and induces the dimerization of a second receptor subunit, gp130. IL‐6 also binds to soluble IL‐6R, and this complex interacts with gp130, regardless of IL‐6R expression. This allows cells that do not express IL‐6R and would be otherwise insensitive to IL‐6 to respond to it. We have generated a constitutively active version of gp130 by forced leucine‐zipper‐mediated dimerization, named L‐gp130. Once inserted into the Rosa26 locus of mice, L‐gp130 can be activated in a cell‐autonomous manner by crossing these mice with any Cre‐recombinase transgenic mouse strain. Activation of gp130 in hepatocytes produced liver‐specific effects such as the induction of acute‐phase proteins, but it also had profound systemic effects on the immune system. Such local and systemic effects of interleukin‐6 will be reviewed.
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