Effect of H2 treatment in a mouse model of rheumatoid arthritis-associated interstitial lung disease

Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD), a primary cause of mortality in patients with RA, has limited treatment options. A previously established RA model in D1CC transgenic mice aberrantly expressed major histocompatibility complex class II genes in joints, developing collagen II-induced polyarthritis and anti-cyclic citrullinated peptide antibodies and interstitial pneumonitis, similar to those in humans. Molecular hydrogen (H-2) is an efficient antioxidant that permeates cell membranes and alleviates the reactive oxygen species-induced injury implicated in RA pathogenesis. We used D1CC mice to analyse chronic lung fibrosis development and evaluate H-2 treatment effects. We injected D1CC mice with type II collagen and supplied them with H-2-rich or control water until analysis. Increased serum surfactant protein D values and lung densities images were observed 10 months after injection. Inflammation was patchy within the perilymphatic stromal area, with increased 8-hydroxy-2MODIFIER LETTER PRIME-deoxyguanosine-positive cell numbers and tumour necrosis factor-alpha, BAX, transforming growth factor-beta, interleukin-6 and soluble collagen levels in the lungs. Inflammatory and fibrotic changes developed diffusely within the perilymphatic stromal area, as observed in humans. H-2 treatment decreased these effects in the lungs. Thus, this model is valuable for studying the effects of H-2 treatment and chronic interstitial pneumonia pathophysiology in humans. H-2 appears to protect against RA-ILD by alleviating oxidative stress.