A high level of prostaglandin E2 (PGE2) in the portal vein suppresses liver-associated immunity and promotes liver metastases.

Abstract:

:Prostaglandin E2 (PGE2) is generally accepted to be an immunosuppressant produced by cancer cells and their surrounding macrophages. Although several investigators have reported detecting high concentrations of PGE2 in the portal veins of patients with colorectal cancer, the relationship between these high concentrations of PGE2 in the portal vein and liver-associated immunity remains unclear. In this study, we attempted to determine if the portal administration of PGE2 suppresses the immune function of the liver in a rat model. Donryu rats were administered PGE2 via the portal vein for 7 days, following which the cytotoxic activity of hepatic sinusoidal lymphocytes (HSL) against natural killer (NK)-sensitive YAC-1 and rat syngeneic AH60C tumor cells was assessed. Purified HSL are spontaneously cytolytic; however, the continuous administration of PGE2 dramatically suppressed the cytotoxic activity of HSLs in a dose-dependent fashion. Flow cytometric analysis showed that the large granular lymphocyte (LGL) fraction, hepatic natural killer (pit) cells, and CD4-8+ killer/suppressor T cells were mainly reduced in number in the HSLs following PGE2 infusion. In this rat AH60C metastasis model, the continuous administration of PGE2 increased the number and size of metastatic tumor nodules in the liver, suggesting that high concentrations of PGE2 in the portal vein suppress liver-associated immunity and promote the formation of hepatic metastasis.

journal_name

Surg Today

journal_title

Surgery today

authors

Okuno K,Jinnai H,Lee YS,Nakamura K,Hirohata T,Shigeoka H,Yasutomi M

doi

10.1007/BF00312380

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

954-8

issue

11

eissn

0941-1291

issn

1436-2813

journal_volume

25

pub_type

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