Effect of Htreatment in a mouse model of rheumatoid arthritis-associated interstitial lung disease.

Abstract

Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is a leading cause of death in RA patients, yet available interventions remain scarce. Using D1CC transgenic mice that aberrantly express MHC class II genes and develop collagen II-induced polyarthritis resembling human RA, this study examined the progression of chronic lung fibrosis and the influence of hydrogen-rich water. Mice received type II collagen injections and were supplied either hydrogen-rich or control water for 10 months. At endpoint, elevated serum surfactant protein D and increased lung density were observed. Lung tissue showed higher numbers of 8-hydroxy-2'-deoxyguanosine-positive cells alongside elevated TNF-α, BAX, TGF-β, IL-6, and soluble collagen levels, with patchy inflammation concentrated in perilymphatic stromal regions. Hydrogen-rich water administration reduced all these pathological markers. The findings indicate that oxidative stress attenuation by molecular hydrogen may underlie its protective role against RA-ILD progression in this model.

Mechanism

Molecular hydrogen permeates cell membranes and scavenges reactive oxygen species, thereby reducing 8-OHdG formation and suppressing TNF-α, TGF-β, IL-6, and BAX upregulation, which collectively attenuates pulmonary inflammation and fibrosis in RA-associated ILD.