TNF Receptor p55 Plays a Major Role in Centrally Mediated Increases of Serum IL-6 and Corticosterone after Intracerebroventricular Injection of TNF

Fabio Benigni, Raffaella Faggioni, Marina Sironi, Giamila Fantuzzi, Peter Vandenabeele, Nozomi Takahashi, Silvano Sacco, Walter Fiers, Wim A. Buurman, Pietro Ghezzi

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Abstract

The aim of this work was to study the relative role of the two TNF receptors (p55 and p75) in the central actions of TNF, studying the elevation of serum corticosterone (CS) and IL-6 levels after injection of recombinant murine (rm)TNF (intracerebroventricularly (i.c.v.)) in normal or p55-deficient (p55 -/-) mice. rmTNF induced high serum IL-6 levels and doubled serum CS in normal mice, whereas no elevation of serum IL-6 or CS was induced in p55 -/- mice. However, a normal CS response was observed in p55 -/- mice after LPS (2.5 μg, i.c.v.). p55 -/- mice also responded, although to a lesser extent than p55 +/+, in terms of LPS-induced IL-6 production. We also injected two agonist Abs specific for the two receptors, αp55 and αp75. While αp55 injected i.c.v. induced a marked elevation in CS and IL-6, αp75 induced CS (although less than αp55) but no IL-6. rmTNF, which binds both receptors, was more potent in inducing IL-6 and CS than injection of rhTNF, which in mice binds only p55. Finally, we investigated the role of p55 and p75 in IL-6 induction by TNF in a murine brain endothelioma. The results resembled closely those obtained in vivo: rmTNF was more potent than rhTNF and only αp55, and not αp75, induced IL-6 production. These data indicate that p55 plays a major role in TNF activation of the hypothalamus-pituitary-adrenal axis and in the centrally mediated induction of peripheral IL-6 by TNF, but p75, despite having little IL-6 inductive properties by itself, seems to potentiate p55 induction of IL-6.

Original languageEnglish
Pages (from-to)5563-5568
Number of pages6
JournalJournal of Immunology
Volume157
Issue number12
Publication statusPublished - Dec 15 1996

ASJC Scopus subject areas

  • Immunology

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    Benigni, F., Faggioni, R., Sironi, M., Fantuzzi, G., Vandenabeele, P., Takahashi, N., Sacco, S., Fiers, W., Buurman, W. A., & Ghezzi, P. (1996). TNF Receptor p55 Plays a Major Role in Centrally Mediated Increases of Serum IL-6 and Corticosterone after Intracerebroventricular Injection of TNF. Journal of Immunology, 157(12), 5563-5568.