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

Interferon (IFN)λ, also known as IL-28A, IL-28B or IL-29, is a new type III IFN, which like type I IFN(α/β), activates common elements of the JAK/STAT signaling pathway and exhibits antiproliferative activity. Currently, IFNα 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 IFNλ induced the same level of cell growth inhibition relative to IFNα. To this effect HaCaT cells, which are typically growth inhibited by IFNα, underwent apoptosis in response to IFNλ. Next, in contrast to IFNα stimulation, IFNλ prolonged the duration of activated STAT1 and STAT2. Furthermore, the kinetics of IFN-stimulated genes was different as IFNλ induced a delayed but stronger induction of IFN-responsive genes. Components of the JAK/STAT pathway remained essential for the antiproliferative effects of IFNα and IFNλ. IFNλ-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 IFNλ signaling is different from that of IFNα, and that IFNλ could be a suitable cytokine to evaluate for cancer therapy.