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


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.
Kawamoto
Shin-ichiro
S
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Oritani
Kenji
K
Asakura
Eiji
E
Ishikawa
Jun
J
Koyama
Mamoru
M
Miyano
Kenmi
K
Iwamoto
Minori
M
Yasuda
Shin-ichiro
S
Nakakubo
Hirosi
H
Hirayama
Fumihiro
F
Ishida
Naoko
N
Ujiie
Hidetoshi
H
Masaie
Hiroaki
H
Tomiyama
Yoshiaki
Y
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects*; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology* / Q000633:toxicity; D006410:Hematopoiesis / Q000187:drug effects; D016898:Interferon-alpha / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D016207:Cytokines; D016898:Interferon-alpha; C410906:limitin