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

Abstract

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-alpha/beta receptor, its signal transduction pathways to express the antiviral effects are different from those of IFN-alpha. To clarify the characteristics of limitin, we compared the biological activities of limitin, such as the antiviral, immunomodulatory, antitumor, and myelosuppressive effects, with IFN-alpha.

MATERIALS AND METHODS:

Limitin and IFN-alpha 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-alpha.

RESULTS:

Limitin had relatively higher antiviral activity than IFN-alpha. 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-alpha. Nevertheless, the treatment of mice with limitin showed neither myelosuppression nor fever that are common adverse effects of IFN-alpha.

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.

• Authors: Shin-ichiro Kawamoto, Kenji Oritani, Eiji Asakura, Jun Ishikawa, Mamoru Koyama, Kenmi Miyano, Minori Iwamoto, Shin-ichiro Yasuda, Hirosi Nakakubo, Fumihiro Hirayama, Naoko Ishida, Hidetoshi Ujiie, Hiroaki Masaie, Yoshiaki Tomiyama
• Journal: Experimental hematology (Exp Hematol) Vol. 32 Issue 9 Pg. 797-805 (Sep 2004) ISSN: 0301-472X [Print] Netherlands
• PMID: 15345280 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antineoplastic Agents
• Cytokines
• Interferon-alpha
• limitin

Topics

• Adjuvants, Immunologic (pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Bone Marrow (drug effects)
• Cell Line
• Cytokines (pharmacology, toxicity)
• Hematopoiesis (drug effects)
• Interferon-alpha (pharmacology, toxicity)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL