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

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.

Pathological study of chronic pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): possible association of fibrosis with the development of granulomatous lesions

“…The role of cytokines and oxidative stress markers, IL-1b and inducible iNOS, respectively, has been reported in studies investigating the pathogenesis of pulmonary toxicity induced by crystalline silica [42,43]. Mice genetically deficient (knockout) in IL-1b or iNOS showed significantly reduced silicotic lesions [44].…”

“…Mice genetically deficient (knockout) in IL-1b or iNOS showed significantly reduced silicotic lesions [44]. The generation of IL-1b [43] and nitric oxide [44] was associated with the development of lung lesions including granuloma formation and fibrosis in experimental silicosis. In this study of ASD toxicity, IL-1b and iNOS expression were also demonstrated in both acute and chronic inflammatory lesions, suggesting that secondary released cytokines and oxidative stress generated in lesions may be involved in the development of the acute and chronic lung lesions induced by the intratracheally instilled ASD particles [45].…”

Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats

“…It has been demonstrated that instilled silica increases IL-1β release in BALF and neutralizes IL-1β attenuated silica-induced pulmonary inflammation and fibrosis. 38 An earlier study has reported that the levels of pro-inflammatory cytokines, such as IL-1β and IFN-γ, are significantly increased in BALF following NiONP exposure. 39 In the current study, we found that NiONP exposure significantly increased IL-1β protein expression in BALF and mRNA expression in AMs.…”

Anakinra and etanercept prevent embryo loss in pregnant nonobese diabetic mice

“…However, anakinra and etanercept made the R837-and CpG-induced increase in embryo resorption to decline almost completely. These findings suggested that anakinra and etanercept may be useful to prevent pregnancy failure in cases of combined bacterial and viral infection (Chen et al 1998, McCall et al 2012, Guo et al 2013.…”