# Modulation of the NF-κB signaling pathway by the combined strategy of tocilizumab and dexamethasone for asthma therapy

## TL;DR

Combining tocilizumab with a reduced dose of dexamethasone improves asthma treatment by reducing inflammation and oxidative stress while minimizing side effects.

## Contribution

A novel combined therapy using tocilizumab and reduced-dose dexamethasone is proposed for safer asthma treatment.

## Key findings

- The combination therapy improved cell viability and reduced apoptosis in lung epithelial cells under oxidative stress.
- TCZ + DEX suppressed NF-κB signaling and reduced proinflammatory cytokine production in asthma models.
- The therapy improved lung function and reduced airway inflammation and remodeling in an ovalbumin-induced asthma model.

## Abstract

Asthma, a prevalent chronic inflammatory airway disease, is conventionally managed with glucocorticoids (GCs) such as dexamethasone (DEX). However, prolonged DEX use induces adverse effects, including immunosuppression and metabolic disruptions. Tocilizumab (TCZ), a humanized monoclonal antibody with immunomodulatory and anti-inflammatory properties, may enhance therapeutic efficacy while minimizing DEX-related toxicities. Herein, we evaluate a combined therapeutic strategy integrating TCZ with a reduced DEX dose (TCZ + DEX) for asthma management. In lung epithelial cells subjected to hydrogen peroxide-induced oxidative stress, TCZ + DEX improved cell viability, reduced apoptosis, and supported proliferative activity, thereby attenuating oxidative and inflammatory injury. The combination therapy also decreased reactive oxygen species levels, preserved mitochondrial membrane potential, and modulated cell cycle-related gene expression, suggesting protection against oxidative stress–induced bronchial epithelial injury and reversal of DEX-mediated cell cycle arrest. In an ovalbumin-induced asthma model, TCZ + DEX improved lung function, reduced airway inflammation, and attenuated airway remodeling, achieving efficacy comparable to standard-dose DEX despite reduced steroid exposure. Mechanistically, TCZ + DEX was associated with suppression of the nuclear factor kappa B–related inflammatory signaling, thereby attenuating proinflammatory cytokine production. These findings provide preclinical evidence that TCZ + DEX offers a practical and safer therapeutic strategy for asthma, mitigating GC-associated adverse effects and providing insights into novel approaches for other chronic inflammatory diseases.

The online version contains supplementary material available at 10.1186/s12931-025-03458-5.