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Current Trends in Immunology   Volumes    Volume 4 
Functional dissection of tumor necrosis factor in liver, brain and lungs
Rudolf Lucas, Georges E. Grau, Michael A. Matthay, Albrecht Wendel
Pages: 47 - 59
Number of pages: 13
Current Trends in Immunology
Volume 4 

Copyright © 2002 Research Trends. All rights reserved


Tumor necrosis factor (TNF), originally considered as a promising anti-cancer agent, displays high systemic toxicity and a pronounced hepatotoxicity, thus limiting its use for the systemic treatment of cancer. The trimeric TNF ligand, binding to at least two types of receptors, represents one of the most prominent cytokines involved in innate defense against bacterial, fungal, parasitic and viral infections. However, whereas the binding of TNF to TNF receptor 1 was shown to be the crucial in protection against infection, this same receptor was shown to mediate endotoxic shock and hepatotoxicity upon overproduction of the ligand. Likewise, TNF receptor 2 was shown to be implicated in neuroprotective effects of TNF in mice, but it is also essential in the development of experimental cerebral malaria. Apart from its receptor binding sites, TNF also diplays a lectin-like domain that is able to directly kill bloodstream forms of African trypanosomes, and that can activate sodium channels in mammalian cells. In this review, we will address the detrimental versus protective role of TNF and its receptors in the liver, brain and lungs. Moreover, we address the recently discovered pulmonary edema reabsorption activity of the cytokine, mediated by the lectin-like activity of the molecule, that has potential therapeutic applications.

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