A new interferon, limitin, displays equivalent immunomodulatory and antitumor activities without myelosuppressive properties as compared with interferon-α

Objective Limitin is a new member of type I interferon (IFN) identified with an expression cloning based on the growth suppression of a myelomonocytic leukemia cell line WEHI3. Although limitin uses the IFN-α/β receptor, its signal transduction pathways to express the antiviral effects are different from those of IFN-α. To clarify the characteristics of limitin, we compared the biological activities of limitin, such as the antiviral, immunomodulatory, antitumor, and myelosuppressive effects, with IFN-α. Materials and Methods Limitin and IFN-α were titered with a cytopathic effect dye binding assay. Induction of MHC class I on a keratinocyte cell line PAM212 was estimated with flow cytometry. Induction of OVA-restricted cytotoxic T lymphocyte (CTL) activity was analyzed with 51Cr release assay. Antiproliferative effects were evaluated with 3H-thymidine incorporation assay using WEHI3 and a lymphoblast cell line L1210. Myelosuppresive effects were evaluated with colony assay. In vivo side effects were estimated after the injection of limitin or IFN-α. Results Limitin had relatively higher antiviral activity than IFN-α. Limitin induced the surface expression of MHC class I, the enhancement of CTL activity, and the growth inhibition of lymphohematopoietic cell lines as strong as IFN-α. Nevertheless, the treatment of mice with limitin showed neither myelosuppression nor fever that are common adverse effects of IFN-α. Conclusions Strong immunomodulatory, antitumor, and antiviral effects with weak myelosuppressive and weak acute toxic effects of limitin indicate that it may be useful as a new therapeutic drug for virus-hepatitis and cancers.