Neutralization of interleukin-1 beta attenuates silica-induced lung inflammation and fibrosis in C57BL/6 mice

Arch Toxicol. 2013 Nov;87(11):1963-1973. doi: 10.1007/s00204-013-1063-z. Epub 2013 May 3.

Abstract

The inflammation and fibrosis induced by silica dust are considered to be substantial responses in silicosis progression. Interleukin-1 beta (IL-1β) plays an important role in silica-induced lung inflammation, but the mechanisms that underlie the influence of IL-1β on the progression of silicosis remain unclear. In this study, the role of IL-1β in silica-induced inflammation and fibrosis was evaluated by administering a suspension of 2.5-mg silica dust, either with or without 40 μg anti-mouse IL-1β monoclonal antibody (mAb), to the lungs of male C57BL/6 mice. Silica + anti-IL-1β mAb-treated mice showed the depletion of IL-1β as well as the attenuation of inflammation, as evaluated in the bronchoalveolar lavage fluid (BALF) and histological sections from 1 to 84 days after silica exposure. Further study of the BALF indicated that inhibition of IL-1β could reduce the contents of tumor necrosis factor-alpha and monocyte chemoattractant protein-1. The real-time PCR and pathology results showed that the neutralization of IL-1β attenuated silica-induced fibrosis by inhibiting the gene expression of transforming growth factor-beta 1, collagen I and fibronectin. The examination of Th1-cytokine and Th2-cytokine suggested that depletion of IL-1β decelerated the Th1/Th2 balance toward a Th2-dominant response. In conclusion, the present study suggests that the neutralization of IL-1β attenuates silica-induced inflammation and fibrosis by inhibiting other inflammatory and fibrogenic mediators and modulating the Th1/Th2 balance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Collagen Type I / biosynthesis
  • Fibronectins / biosynthesis
  • In Vitro Techniques
  • Interleukin-1beta / antagonists & inhibitors*
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pulmonary Alveoli / pathology
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / pathology
  • Silicon Dioxide / toxicity*
  • Silicosis / drug therapy*
  • Silicosis / pathology
  • Th1-Th2 Balance / drug effects
  • Transforming Growth Factor beta / biosynthesis

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Collagen Type I
  • Fibronectins
  • Interleukin-1beta
  • Transforming Growth Factor beta
  • Silicon Dioxide