'Off-switch' for systemic inflammation

Systemic inflammation helps protects the body until a more specific immune response can be mounted. This process is mediated by several cytokines that act on the liver, but the molecular mechanisms controlling it remain unclear. In February 8 Cell, Joo-Yeon Yoo and colleagues, from Howard Hughes Medical Institute, Baltimore, USA, show that Stat3-β — a transcription factor activated in the liver by the IL-6 family of cytokines — has a critical role in the control of systemic inflammation.

Alternative splicing of the Stat3 gene produces two isoforms: Stat3-α and a dominant-negative variant, Stat3-β. Yoo et al. created Stat3-β deficient mice and observed that mutant mice exhibited diminished recovery from endotoxic shock and chronic hyperresponsiveness of a subset of endotoxin-inducible genes in liver. In addition, they found that the hepatic response to endotoxin in wild-type mice was accompanied by a transient increase in the ratio of Stat3β to Stat3α (Cell 2002, ...