Inhibitors of cytochrome P450 suppress tumor necrosis factor production.

Abstract:

:We tested the effect of different inhibitors of cytochrome P450 on tumor necrosis factor (TNF) production. Metyrapone and SKF525A (100 and 50 mg/kg, ip, respectively) suppressed serum TNF induced by cotreatment with endotoxin (LPS), (2.5 micrograms/mouse). Inhibition was independent of endogenous corticosteroids since it was also observed in adrenalectomized mice. In vitro production of TNF by endotoxin-stimulated human monocytes was also inhibited by metyrapone and SKF525A. Since lipoxygenase (LO) inhibitors also block TNF production and metyrapone was reported to inhibit LO, we suggest that inhibition by metyrapone and SKF525A might be due to inhibition of either LO or a cytochrome P450 implicated in the oxidation of endogenous substrates involved in the inflammatory response.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Fantuzzi G,Cantoni L,Sironi M,Ghezzi P

doi

10.1006/cimm.1993.1209

subject

Has Abstract

pub_date

1993-09-01 00:00:00

pages

417-24

issue

2

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(83)71209-8

journal_volume

150

pub_type

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