Neutralization of IL-6 inhibits formation of autoreactive TH17 cells but does not prevent loss of renal function in experimental autoimmune glomerulonephritis

Immunol Lett. 2021 Aug:236:51-60. doi: 10.1016/j.imlet.2021.05.002. Epub 2021 May 17.


In anti-glomerular basement membrane glomerulonephritis (anti-GBM GN), antibodies and T cells directed against the Goodpasture antigen, the non-collagenous domain of the α3-chain of type IV collagen (α3(IV)NC1), provoke renal inflammation resulting in rapidly progressing crescentic GN. Interleukin 6 (IL-6) is a pleiotropic cytokine with both pro- and anti-inflammatory activities, and IL-6 blockade is successfully used for treatment of diseases associated with acute and chronic inflammation. However, the role of IL-6 in anti-GBM GN is unclear. Here, we use the mouse model of experimental autoimmune glomerulonephritis (EAG) to study the role of IL-6 in anti-GBM GN. DBA/1J mice were immunized with α3(IV)NC1 and developed fatal crescentic GN. Treatment of mice with neutralizing anti-IL-6 antibodies impaired the generation of α3(VI)NC1-specific TH1 and TH17 cells. However, despite lasting reduction of the TH17 cell response, antibody treatment did not prevent crescentic GN. Antibody treatment was also ineffective in a therapeutic setting with pre-existing autoantibodies and T cells. In conclusion, our results indicate that although the blockade of IL-6 impairs the development of autoimmunity against α3(VI)NC1, this treatment does not ameliorate crescentic GN both in a preemptive and a therapeutic approach.

Keywords: Glomerulonephritis; IL-6; Kidney; TH17 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Autoantigens / immunology
  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / etiology*
  • Autoimmune Diseases / metabolism*
  • Autoimmune Diseases / therapy
  • Autoimmunity
  • Biomarkers
  • Collagen Type IV / immunology
  • Disease Models, Animal
  • Disease Susceptibility / immunology
  • Glomerulonephritis / diagnosis
  • Glomerulonephritis / etiology*
  • Glomerulonephritis / metabolism*
  • Glomerulonephritis / therapy
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Interleukin-6 / antagonists & inhibitors*
  • Kidney Function Tests
  • Mice
  • Organ Specificity / immunology
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism*


  • Antibodies, Monoclonal
  • Autoantigens
  • Biomarkers
  • Collagen Type IV
  • Interleukin-6
  • type IV collagen alpha3 chain