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

Biochem Pharmacol. 2001 Oct 15;62(8):1141-4. doi: 10.1016/s0006-2952(01)00757-2.

Abstract

Although changes in airway responsiveness in pulmonary inflammation are commonly related to the action of infiltrated leukocytes, our previous report suggested a direct role of inflammatory cytokines in LPS-induced lung hyporesponsiveness. 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 induced a time-dependent increase in IL-(interleukin-)1beta, IL-6, and TNF (tumor necrosis factor)alpha in the BALF. Cytokine production was paralleled by 5-HT lung hyporesponsiveness, and intratracheal administration of TNFalpha proved to be very efficient in inhibiting 5-HT responsiveness. In addition, systemic treatment with rolipram, an inhibitor of TNFalpha production, was paralleled by a significant recovery of lung responsiveness. On the contrary, IL-1beta and IL-6 were not demonstrated to play a relevant role in 5-HT hyporesponsiveness. It is concluded that TNFalpha could be a crucial mediator of LPS-induced lung hyporesponsiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Bronchoalveolar Lavage Fluid
  • Endotoxins / pharmacology*
  • Female
  • Interleukin-1 / physiology
  • Interleukin-6 / physiology
  • Lipopolysaccharides / pharmacology*
  • Lung / drug effects*
  • Lung / pathology
  • Lung / physiopathology
  • Mice
  • Models, Animal
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Endotoxins
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha