Sepsis is one of the main causes of death in the intensive care unit. When an infection becomes severe, the immune system misfires, triggering a cascade of inflammatory responses. Pro-inflammatory factors secreted by immune cells called macrophages enhance the damage, worsening the clinical picture, and while interventions for sepsis are available, mortality remains high. Now, researchers have identified a new target in the battle against sepsis. Using cells isolated from mice, they measured gene and protein expression during E. coli challenge. They found that cytochrome P450 1A1 (CYP1A1), an enzyme that regulates metabolism, also regulates inflammatory responses during sepsis. CYP1A1 directed macrophages to initiate a microbe-internalizing process, phagocytosis, during infection. Inhibiting CYP1A1 blocked phagocytosis of bacteria in macrophages, preventing the cells from secreting more inflammatory molecules. This strategy was also effective in a mouse model of sepsis. The results identify CYP1A1 as a novel target to inhibit macrophage-driven inflammation, poising it as a promising potential treatment for inflammatory diseases and sepsis.