A genome-wide analysis of the acute-phase response and its regulation by Stat3β

The acute-phase response (APR) is the systemic inflammatory component of innate immunity. A global assessment of hepatic gene expression during an APR has been undertaken. In response to endotoxin, an inducer of the APR, about 7% of mouse genes exhibited significant changes in expression. Genes for cholesterol, fatty acid, and phospholipid synthesis were suppressed, while genes participating in innate defense and antigen presentation were induced. Upon challenge with endotoxin, mice deficient in Stat3β, a dominant-negative variant of Stat3, exhibited impaired recovery and susceptibility to protracted shock. These findings are accompanied by overexpression and hyperresponsiveness of a subset of lipopolysaccharide (LPS)-inducible genes in liver, suggesting a critical role for Stat3β in the control of systemic inflammation.