Interleukin 4 inhibits stimulation of hepatic lipogenesis by tumor necrosis factor, interleukin 1, and interleukin 6 but not by interferon-alpha.

Abstract:

:Multiple cytokines stimulate hepatic lipogenesis in rodents. We have previously shown that lipogenic cytokines can be divided into 2 classes by their mechanism of action and their synergistic interactions. We now report the effects of interleukin 4, a cytokine known to inhibit the synthesis and action of other cytokines. Interleukin 4 by itself did not alter hepatic lipogenesis. However, interleukin 4 inhibited the characteristic stimulation of hepatic lipogenesis that is seen with tumor necrosis factor, interleukin 1, and interleukin 6. These 3 cytokines stimulate hepatic lipogenesis by the same mechanism, increasing hepatic levels of citrate, a key allosteric activator of acetyl CoA carboxylase, the rate-limiting enzyme of fatty acid synthesis. Interleukin 4 blocks the ability of tumor necrosis factor to increase hepatic citrate. In contrast, interleukin 4 does not block the stimulation of hepatic lipogenesis by interferon-alpha, a cytokine that increases hepatic lipogenesis by a mechanism other than increasing hepatic citrate levels. These results demonstrate that interleukin 4 can inhibit the metabolic action of selected cytokines, which provides strong support for our proposal that lipogenic cytokines operate through 2 distinct mechanisms of action and can therefore be divided into 2 separate classes based on their interactions. These results also emphasize the multiple relationships between the immune response and lipid metabolism.

journal_name

Cancer Res

journal_title

Cancer research

authors

Grunfeld C,Soued M,Adi S,Moser AH,Fiers W,Dinarello CA,Feingold KR

subject

Has Abstract

pub_date

1991-06-01 00:00:00

pages

2803-7

issue

11

eissn

0008-5472

issn

1538-7445

journal_volume

51

pub_type

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