Neutralizing the Th1 effector cytokines, IFN-γ and TNF-α, attenuates established experimental autoimmune anti-myeloperoxidase glomerulonephritis.

ABSTRACT:

Introduction

This study investigates the therapeutic potential of blocking key CD4⁺ Th1 effector cytokines, TNF-α and IFN-γ, in experimental anti-myeloperoxidase (MPO) glomerulonephritis (GN). The immunopathogenesis of MPO autoimmunity is biphasic, with an initial transient Th17 dominance followed by a sustained Th1 response, posing challenges for effective cytokine blockade.

Methods

To evaluate anti-cytokine therapy at distinct disease phases, we induced anti-MPO autoimmunity in mice through MPO immunization and triggered GN using anti-glomerular basement membrane (GBM) globulin at early (day 20) and late (days 32 and 38) stages. Mice received anti-TNF-α or anti-IFN-γ beginning 4 hours post-GN induction, with kidney injury assessed 4 or 10 days later.

Results<

SUBMITTER: Nagai K 

PROVIDER: S-EPMC12305698 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature