TNF and Hepatitis: Earlier studies have demonstrated that the secretion of TNF-α and its binding to TNFR-I are essential for both lethality and hepatic injury in LPS-induced hepatitis.28 Higher levels of LPS-induced hepatic TNF-α and other pro-inflammatory cytokines, such as IL-1β and IL-6, were observed in Per1−/− mice compared with WT mice, leading to more prominent liver damage and lethality in Per1−/− mice.