Role of tumor necrosis factor-alpha in endotoxin-induced lung parenchymal hyporesponsiveness in mice

Citation
L. Brandolini et al., Role of tumor necrosis factor-alpha in endotoxin-induced lung parenchymal hyporesponsiveness in mice, BIOCH PHARM, 62(8), 2001, pp. 1141-1144
Citations number
15
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
8
Year of publication
2001
Pages
1141 - 1144
Database
ISI
SICI code
0006-2952(20011015)62:8<1141:ROTNFI>2.0.ZU;2-D
Abstract
Although changes in airway responsiveness in pulmonary inflammation are com monly related to the action of infiltrated leukocytes, our previous report suggested a direct role of inflammatory cytokines in LPS-induced lung hypor esponsiveness. The aim of this study was to define if cytokines detected in the BALF (bronchoalveolar lavage fluid) of intratracheal LPS-treated mice could be, at least in part, responsible for 5-HT (5-hydroxytryptamine) lung hyporeactivity. Our results show that intratracheal instillation of LPS in duced a time-dependent increase in IL-(interleukin-)1 beta, IL-6, and TNF ( tumor necrosis factor)alpha in the BALF. Cytokine production was paralleled by 5-HT lung hyporesponsiveness, and intratracheal administration of TNF a lpha proved to be very efficient in inhibiting 5-HT responsiveness. In addi tion, systemic treatment with rolipram, an inhibitor of TNF alpha productio n, was paralleled by a significant recovery of lung responsiveness. On the contrary, IL-1 beta and IL-6 were not demonstrated to play a relevant role in 5-HT hyporesponsiveness. It is concluded that TNF alpha could be a cruci al mediator of LPS-induced lung hyporesponsiveness. (C) 2001 Elsevier Scien ce Inc. All rights reserved.