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 9weeks. 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-, 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.
[1]Natl Res Inst Child Hlth & Dev, Div Transplantat Immunol, Tokyo, Japan;
[2]Guangdong Acad Med Sci, Guangdong Cardiovasc Inst, Guangdong Gen Hosp, Guangzhou, Guangdong, Peoples R China;
[3]Fudan Univ, Inst Rheumatol Immunol & Allergy, 12 Wulumuqi Middle Rd, Shanghai 200040, Peoples R China;
[4]Fudan Univ, Huashan Hosp, Dept Rheumatol, Shanghai, Peoples R China;
[5]Natl Inst Infect Dis, AIDS Res Ctr, Tokyo, Japan;
[6]SBI Pharmaceut Co Ltd, Tokyo, Japan
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