Subcutaneous administration of infliximab-attenuated silica-induced lung fibrosis

Abstract

Objectives: To investigate the influence of the anti-tumor necrosis factor-α infliximab (IFX) in the case of rats with silicosis. Material and Methods: Forty-eight Wistar rats were randomly divided into 3 groups. The study group (N = 16) -silicosis was induced by intratracheal instillation of 50 mg silica on day 1, and IFX was subcutaneously administered at a dose of 15 mg/kg of body weight from day 2 to day 6, the vehicle group (N = 16) -silica used as the study group but without IFX, the sham group (N = 16) -1 ml of saline was intratracheal-used. Eight rats in each group were euthanized on day 7 and on day 14, respectively. Lung tissue sections were stained with hematoxylin and eosin or Masson's trichromedye. The nuclear factor-κB p65 (NF-κB p65) positioning in the lung tissues were determined by immunohistochemical staining. Levels of tumor necrosis factor α (TNF-α) in rat serum and bronchoalveolar lavage fluid were measured with enzyme linked immunosorbent assay. The inducible nitric oxide synthase (iNOS) mRNA in the lung tissues was measured by quantitative real-time polymerase chain reaction, as well as inhibitor protein-κB (I-κB) and NF-κB p65 expression were measured quantitatively by western blotting. Results: Silica installation increased the lung tissues inflammation reaction, oxidative stress and pulmonary fibrosis. Infliximab treatment significantly improved silica-induced lung pathological changes (inflammatory cells, collagen deposition), decreased the TNF-α inhibited NF-κB signaling (I-κB, NF-κB p65) as well as oxidant status (iNOS). Conclusions: Infliximab may improve silica-induced pulmonary inflammation by decreasing the TNF-α, inhibiting NF-κB signaling (I-κB, NF-κB p65) as well as oxidant status (iNOS), which suggest that IFX has potential role in the treatment of silica-induced lung damage. Int J Occup Med Environ Health 2018;31(4):503 -515

Tumor necrosis factor gene polymorphisms are associated with silicosis: a systemic review and meta-analysis

“…TNF pro-inflammatory cytokine overexpression and involvement in silica-induced sponge collagen biosynthesis was demonstrated in quartz-treated explants as compared with controls by means of specific TNF inhibitors affecting the fibrogenic gene response [36]. Zhang et al have found that anti-TNF may improve silica-induced pulmonary inflammation by decreasing the TNF-α, inhibiting NF-κB signaling as well as oxidant status, which suggest that anti-TNF has potential role in the treatment of silica-induced lung damage [37]. On the other hand, several studies discussed association of TNF gene polymorphisms in patients with silicosis, but results were inconsistent.…”

Inhibition of tumor necrosis factor-α enhanced the antifibrotic effect of empagliflozin in an animal model with renal insulin resistance

“…In addition to its inflammatory role, it stimulates the release of TGF-β1 and has an important role in glomerular inflammation and fibrosis [18]. Previous studies on different models of fibrosis showed that Infliximab (IFX), a monoclonal antibody for TNF-α [19], attenuates effectively the fibrosis and the induced inflammation via decreasing the TNF-α and inhibiting nuclear factor kappa-B, NF-κB [20,21]. However its effect on improving RF induced by IR has not been studied yet.…”

New Insights into Pathomechanisms and Treatment Possibilities for Lung Silicosis

“…In silica-and bleomycin-induced mice models of pulmonary fibrosis, infusion of a human recombinant soluble TNF receptor (rsTNFR-β), which acts as a TNFα antagonist, decreased biochemical markers of lung fibrosis (contents of hydroxyproline and collagen), reduced the proportion of areas in the damaged lung and, in the silicosis model, diminished the formation of nodules with rich collagen contents [100]. Administration of infliximab, a monoclonal immunoglobin G neutralizing TNFα biological activity, to rats with silica-induced acute lung injury significantly improved lung pathological changes, decreased the count of inflammatory cells and collagen deposition, declined TNFα in serum and BALF, and suppressed NF-κB signaling and expression of inducible NOS [102]. Similarly, pretreatment with infliximab in bleomycin-instilled rats effectively prevented them from inflammation, oxidative stress, and lung fibrosis [101].…”