In this study, we identified YB‐1 as an important regulator of the immune regulatory cytokine IL‐10 via its fourth intron region in endotoxemia and in I/R‐induced sterile inflammation and demonstrated that YB‐1 exerts both pro‐ and anti‐inflammatory properties in the course of inflammation. The gene discussed is YBX1; the disease is serum lipopolysaccharide activity.