The immunomodulatory quinoline-3-carboxamide paquinimod reverses established fibrosis in a novel mouse model for liver fibrosis

PLoS One. 2018 Sep 5;13(9):e0203228. doi: 10.1371/journal.pone.0203228. eCollection 2018.

Abstract

Quinoline-3-carboxamides (Q substances) are small molecule compounds with anti-inflammatory properties. In this study, we used one of these substances, Paquinimod, to treat a novel model for chronic liver inflammation and liver fibrosis, the NOD-Inflammation Fibrosis (N-IF) mouse. We show that treatment of N-IF mice significantly reduced inflammation and resulted in the regression of fibrosis, even when the treatment was initiated after onset of disease. The reduced disease phenotype was associated with a systemic decrease in the number and reduced activation of disease-promoting transgenic natural killer T (NKT)-II cells and their type 2-cytokine expression profile. Paquinimod treatment also led to a reduction of CD115+ Ly6Chi monocytes and CD11b+ F4/80+ CD206+ macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Immunologic Factors / pharmacology*
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Monocytes / pathology
  • Natural Killer T-Cells / drug effects
  • Natural Killer T-Cells / metabolism
  • Natural Killer T-Cells / pathology
  • Quinolines / pharmacology*

Substances

  • Cytokines
  • Immunologic Factors
  • Quinolines
  • quinoline-3-carboxamide

Grant support

This work was supported by (DH) NovoNordisk Fonden, NNF15OC0016146, Diabetesfonden, DIA2017-221, Barndiabetesfonden, and the Lundberg Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.