PAD4^−/− mice are similarly susceptible to bacteremia in polymicrobial sepsis as their PAD4^+/+ littermates during high-grade CLP. Mice were subjected to high-grade CLP. (A) Survival curves indicating similar survival rates of PAD4^−/− mice and their PAD4^+/− or PAD4^+/+ littermates in high-grade CLP. (B) Bacterial CFUs were quantified from the blood, liver, and lung 18 hours after high-grade CLP to determine systemic bacteremia and were not significantly different between genotypes. (C) Loss of body temperature was similar in PAD4^−/− mice and their littermates. (D) High-grade CLP resulted in higher increases in plasma DNA in PAD4^+/+ or PAD4^+/− mice compared with PAD4^−/− mice. (E-F) Cytokine levels in the plasma of mice. IL-6 (E) and IL-10 (F) were similarly produced in mice of all genotypes; n = 4-8. (G) Survival curve of PAD4^+/+ or PAD4^−/− mice that were given the broad-spectrum antibiotic imipenem/cilastatin 4 to 6 hours after CLP. Mortality was accelerated in the PAD4^−/− mice (P = .043). (H) Bacterial CFUs were not statistically different between PAD4^+/+ or PAD4^−/− mice in the blood, liver, or lung 24 hours after CLP. NS, not significant. PAD4^+/+, black; PAD4^+/−, blue; and PAD4^−/−, red.