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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\u2009+\u2009DEX) for asthma management. In lung epithelial cells subjected to hydrogen peroxide-induced oxidative stress, TCZ\u2009+\u2009DEX 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\u2013induced bronchial epithelial injury and reversal of DEX-mediated cell cycle arrest. In an ovalbumin-induced asthma model, TCZ\u2009+\u2009DEX improved lung function, reduced airway inflammation, and attenuated airway remodeling, achieving efficacy comparable to standard-dose DEX despite reduced steroid exposure. Mechanistically, TCZ\u2009+\u2009DEX was associated with suppression of the nuclear factor kappa B\u2013related inflammatory signaling, thereby attenuating proinflammatory cytokine production. These findings provide preclinical evidence that TCZ\u2009+\u2009DEX 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.<\/jats:p>","DOI":"10.1186\/s12931-025-03458-5","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:04:35Z","timestamp":1767866675000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of the NF-\u03baB signaling pathway by the combined strategy of tocilizumab and dexamethasone for asthma therapy"],"prefix":"10.1186","volume":"27","author":[{"given":"Xinyi","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihui","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qihui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"issue":"1","key":"3458_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01344-4","volume":"8","author":"J Wang","year":"2023","unstructured":"Wang J, Zhou Y, Zhang H, Hu L, Liu J, Wang L, et al. 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