Research ArticleImmunology

A leukotriene-dependent spleen-liver axis drives TNF production in systemic inflammation

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Science Signaling  20 Apr 2021:
Vol. 14, Issue 679, eabb0969
DOI: 10.1126/scisignal.abb0969

Inflamed from afar

The spleen is thought to be the major source of the proinflammatory cytokine TNF during systemic inflammation. However, Fonseca et al. found that the liver and lungs produced more TNF than did the spleen in response to LPS-induced systemic inflammation in rats. Experiments with splenectomized and hepatectomized animals and isolated tissue-resident macrophages showed that much of the spleen-dependent, LPS-induced increase in circulating TNF also depended on the production of TNF by Kupffer cells, the resident macrophages of the liver. Liver TNF production was enhanced in vivo and in vitro by leukotriene B4 (LTB4) released by the spleen. Together, these findings implicate LTB4 as a spleen-derived endocrine signal that promotes the hepatic production of TNF during systemic inflammation.

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