Interestingly, while TRAIL administration did not induce hepatitis in Ripk1 <sup>LPC-KO</sup> mice or in their WT counterparts, its combination with IFN-γ only induced TNF-α dependent apoptosis in the Ripk1 <sup>LPC-KO</sup> mice.
In the mouse model of Con A-induced hepatitis, where death of mouse hepatocytes is dependent on TRAIL and NKT (Natural Killer T) cells, PARP-1 activity was positively correlated with liver injury and hepatitis was prevented both by Nec-1 or PJ-34.
We propose that, in myeloid cells, the differential activation of p38 and NF-κB and induction of TRAIL, which sensitizes cells to apoptosis, can help to explain differences in responsiveness to IFN-β therapy among patients with RRMS and, furthermore, that such differential patterns of activation and expression may also be important in understanding the therapeutic responses to IFN-α/β in hepatitis and cancer.