FVIIa attenuates LPS-induced inflammatory cytokine elaboration in the lung and kidney tissues of the mice in EPCR-dependent fashion. WT C57 BL/6J, EPCR-overexpressing (Tie2-EPCR), or EPCR-deficient (EPCR-def) mice were administered with saline or human FVIIa (250 µg/kg body weight) IV via the tail vein. After 2 hours, the mice receiving saline were left either unchallenged (saline) or administered with LPS (5 mg/kg; LPS) intraperitoneally. The same dose of LPS was administered in parallel to mice injected with FVIIa. Six hours following LPS administration, the mice were killed by exsanguination, perfused with saline to remove blood, and the lung and kidney tissues were collected. The tissues were homogenized in the RIPA buffer containing protease inhibitors and centrifuged at 10 000g at 4°C to remove tissue debris. The supernatants were used to measure the cytokines by ELISA. The cytokines measured were TNF-α (A,E), IL-1β (B,F), IL-6 (C,G), and CCL2 (D) in lung tissue (A-D) and kidney tissue (E-G). Data represent mean ± SEM of 3 independent experiments, a total of 6 to 9 animals in a group. *P < .05; **P < .01; ns, not statistically significant.