ONO-4007, a synthetic lipid A analog, induces Th1-type immune response in tumor eradication and restores nitric oxide production by peritoneal macrophages.

Abstract:

:We have reported that ONO-4007, a novel synthetic lipid A derivative with low toxic activities, produced large amount of tumor necrosis factor (TNF)-alpha selectively in the tumor tissues and brought about complete cures in about 60% of rats bearing TNF-alpha sensitive KDH-8 cells, which also secreted a large amount of transforming growth factor (TGF)-beta. In our present study, to explore ONO-4007 induced Th1-type immune response, we investigated the mRNA expression of interferon (IFN)-gamma, Interleukin (IL)-1beta, IL-6, IL-10, IL-12 in KDH-8 bearing rats. We next examined the nitric oxide (NO) production. We found that IFN-gamma, IL-1beta, IL-6 and IL-12 mRNA expression of the tumor tissue were higher in the ONO-4007 treated rats than in phosphate buffer saline (PBS) treated rats. Western blotting also revealed that IL-12 protein production was increased. NO production from peritoneal macrophages were suppressed in tumor-bearing rats, but ONO-4007 restored it up to the normal level. These results suggest that ONO-4007 induces and restores Th1-type immune response through cytokine production cascade, followed by initial TNF-alpha production, eventually leading to tumor eradication.

journal_name

Int J Oncol

authors

Matsushita K,Kuramitsu Y,Ohiro Y,Kobayashi I,Watanabe T,Kobayashi M,Hosokawa M

keywords:

subject

Has Abstract

pub_date

2003-08-01 00:00:00

pages

489-93

issue

2

eissn

1019-6439

issn

1791-2423

journal_volume

23

pub_type

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