Iguratimod reduces B-cell secretion of immunoglobulin to play a protective role in interstitial lung disease

Int Immunopharmacol. 2021 Aug:97:107596. doi: 10.1016/j.intimp.2021.107596. Epub 2021 Apr 20.

Abstract

Objective: Our study aimed to investigate the effect of Iguratimod (IGU) on bleomycin (BLM)-induced interstitial lung disease (ILD).

Methods: The pulmonary fibrosis model group mice were developed by intratracheal injection of BLM. Mice were divided into two groups at random: (1) Control group (BLM group) - endotracheal BLM (BLM, 3.5 mg/kg, Kayaku, Japan) plus an intraperitoneal injection of normal saline, and (2) BLM + IGU group - intratracheal BLM (same as the control group) + IGU intraperitoneal injection (50 mg/kg/d). The alveolar lavage fluid, histopathology/immunohistochemistry, imaging, and other tests were performed on days 7, 14, 21, and 28 after injection.

Results: Lung function, including Compliance (Crs),Tissue damping (G), Static compliance (Cst), Inspiratory capacity (IC), Elastance (Ers), Tissue elastance (H) and Respiratory system resistance (Rrs) in mice, was improved by IGU. IGU reduced BLM-induced changes in pulmonary fibrosis and pulmonary inflammation, as shown in histological examination.Collagen production and inflammatory damage in the lungs caused by BLM were also reduced by IGU. IGU reduced the expression of immunoglobulin IgG and type I collagen in BLM-induced pulmonary fibrosis mice by inhibiting the production of B cells and immunoglobulin, and also delayed the deterioration of imaging changes.

Conclusion: IGU inhibits immunoglobulin secretion by B cells to relieve pulmonary inflammation and fibrosis. IGU also plays a protective role in the lung in ILD.

Keywords: B-cell; Iguratimod; Immunoglobulin; Interstitial lung disease.

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Bleomycin / adverse effects
  • Chromones / pharmacology*
  • Chromones / therapeutic use
  • Disease Models, Animal
  • Humans
  • Immunoglobulins / metabolism
  • Lung / drug effects
  • Lung / immunology
  • Lung / pathology
  • Lung Diseases, Interstitial / chemically induced
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / immunology
  • Lung Diseases, Interstitial / pathology
  • Mice
  • Sulfonamides / pharmacology*
  • Sulfonamides / therapeutic use

Substances

  • Chromones
  • Immunoglobulins
  • Sulfonamides
  • Bleomycin
  • iguratimod