IL-38: A new factor in rheumatoid arthritis

• Published in: Biochemistry and biophysics reports 2015-12, Vol.4, p.386-391
• Main Authors: Takenaka, Shin-Ichi, Kaieda, Shinjiro, Kawayama, Tomotaka, Matsuoka, Masanobu, Kaku, Yoichiro, Kinoshita, Takashi, Sakazaki, Yuki, Okamoto, Masaki, Tominaga, Masaki, Kanesaki, Katsuya, Chiba, Asako, Miyake, Sachiko, Ida, Hiroaki, Hoshino, Tomoaki
• Format: Article
• Language: English
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2015.10.015

The newly characterized cytokine IL-38 (IL-1F10) belongs to the IL-1 family of cytokines. Previous work has demonstrated that IL-38 inhibited -induced IL-17 production from peripheral blood mononuclear cells. However, it is still unclear whether IL-38 is an inflammatory or an anti-inflammatory cytokine. We generated anti-human IL-38 monoclonal antibodies in order to perform immunohistochemical staining and an enzyme-linked immunosorbent assay. While human recombinant IL-38 protein was not cleaved by recombinant caspase-1, chymase, or PR3 in vitro, overexpression of IL-38 cDNA produced a soluble form of IL-38 protein. Furthermore, immunohistochemical analysis showed that synovial tissues obtained from RA patients strongly expressed IL-38 protein. To investigate the biological role of IL-38, C57BL/6 IL-38 gene-deficient ( ) mice were used in an autoantibody-induced rheumatoid arthritis (RA) mouse model. As compared with control mice, IL-38 mice showed greater disease severity, accompanied by higher IL-1β and IL-6 gene expression in the joints. Therefore, IL-38 acts as an inhibitor of the pathogenesis of autoantibody-induced arthritis in mice and may have a role in the development or progression of RA in humans.