IFNα and IFNλ differ in their antiproliferative effects and duration of JAK/STAT signaling activity

Interferon (IFN)lambda, also known as IL-28A, IL-28B or IL-29, is a new type III IFN, which like type I IFN(alpha/beta), activates common elements of the JAK/STAT signaling pathway and exhibits anti-proliferative activity. Currently, IFN alpha is used in the treatment of certain forms of cancer, but its antitumor effects are limited and associated with high toxicity. In this study, we determined whether IFN lambda induced the same level of cell growth inhibition relative to IFN alpha. To this effect HaCaT cells, which are typically growth inhibited by IFN alpha, underwent apoptosis in response to IFN lambda. Next, in contrast to IFN alpha stimulation, IFN lambda prolonged the duration of activated STAT1 and STAT2. Furthermore, the kinetics of IFN-stimulated genes was different as IFN lambda induced a delayed but stronger induction of IFN-responsive genes. Components of the JAK/STAT pathway remained essential for the antiproliferative effects of IFN alpha and IFN lambda. IFN lambda-induced persistence of STAT activation required de novo protein synthesis and was in part due to a delay in STAT2 inactivation. Thus our data demonstrate that the duration of IFN lambda signaling is different from that of IFN alpha, and that IFN lambda could be a suitable cytokine to evaluate for cancer therapy.