Combination of 5‐aminolevulinic acid and iron prevents skin fibrosis in murine sclerodermatous graft‐versus‐host disease

Scleroderma or systemic sclerosis (SSc) is a clinically heterogeneous rheumatological autoimmune disease affecting the skin, internal organs and blood vessels. There is at present no effective treatment for this condition. Our study investigated the effects of 5‐aminolevulinic acid (5‐ALA), which is a precursor of haem synthesis, on graft‐vs‐host disease (GvHD)‐induced SSc murine model. Lymphocytes were intravenously injected from donor mice (B10.D2) into recipient BALB/c mice (recombination‐activating gene 2 (Rag‐2)‐null mice) deficient in mature T and B cells to induce sclerodermatous GvHD (scl‐GvHD). To investigate the effect of 5‐ALA on scl‐GvHD, combination of 5‐ALA and sodium ferrous citrate (SFC) was orally administered to the recipient mice for 9 weeks. 5‐ALA/SFC treatment significantly reduced progressive inflammation and fibrosis in the skin and ears. Furthermore, 5‐ALA/SFC suppressed mRNA expression of transforming growth factor‐β, type I collagen and inflammatory cytokines. These results indicate that the 5‐ALA/SFC combination treatment has a protective effect against tissue fibrosis and inflammation in a murine scl‐GvHD‐induced skin and ear inflammation and fibrosis. Furthermore, the efficacy of 5‐ALA/SFC suggests important implications of HO‐1 protective activity in autoimmune diseases, and therefore, 5‐ALA/SFC may have promising clinical applications. These findings suggested that the 5‐ALA/SFC treatment may be the potential strategies for SSc.