Interleukin 12 augments the liver-associated immunity and reduces liver metastases.
OBJECTIVE
It has been reported recently that in vivo administration of interleukin-12 (IL-12) augments the cytotoxic activity of natural killer (NK)/T cells and shows a powerful anti-tumor activity. In this study, we evaluated that the IL-12 effect on liver-associated immunity and in vivo efficacy on the hepatic metastases in a rat model.


METHODS
Varying amounts of mouse recombinant IL-12 were injected intraperitoneally for 5 days to adult male Fischer rats and hepatic sinusoidal lymphocytes (HSL) were collected. Purified HSL are spontaneously cytolytic to both conventional NK-sensitive target (YAC-1) and NK-resistant target (RCN-H4) tumor cells.


RESULTS
IL-12 was found to increase the number of HSL and the cytolytic activity against these target cells in a dose-dependent fashion. Flow cytometric analysis showed that IL-12 caused an increase of CD8+ subpopulation in HSL and a double staining study revealed that the increased subpopulation was not CD3+8+ (cytotoxic T cell) fraction, but actually CD3-8+ (NK cell) fraction. Experimental liver metastases was markedly reduced in rats treated intraperitoneally with IL-12.


CONCLUSIONS
These results demonstrate that IL-12 augments the cytolytic activity of HSL and suggests this cytokine as an attractive choice for liver metastases therapy.
First Department of Surgery, Kinki University School of Medicine, Osaka.
K
K
Okuno
H
H
Jinnai
Y S
YS
Lee
K
K
Kaneda
M
M
Yasutomi
D000276:Adjuvants, Immunologic; D000818:Animals; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000276:immunology* / Q000627:therapeutic use; D008099:Liver / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology* / Q000556:secondary* / Q000628:therapy; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D000276:Adjuvants, Immunologic; D018664:Interleukin-12