In vivo anti-inflammatory activities of novel cytokine IL-38 in Murphy Roths Large (MRL)/lpr mice

The newly named interleukin (IL)-36 subfamily member IL-38 has been shown to exert anti-inflammatory activity. However, the in vivo immunomodulatory activity of IL-38 was poorly investigated in systemic lupus erythematosus (SLE). We have investigated the expression of CD4(+)IL-17(+) Th17, CD4(+)IFN-gamma(+) Th1 and CD3(+)CD4(-)CD8(-) double negative (DN) T cells and the related immunopathological mechanisms in female MRL/Ipr mice model of spontaneous lupus-like disease, with or without IL-38 treatment. Intravenous administfation of murine recombinant IL-38 into MRL/Ipr mice can ameliorate the lupus-like clinical symptoms including proteintiria, leukocyteuria and skin lesions. A remission of histopathology characteristics of skin and nephritis was also observed upon IL-38 treatment. Accordingly, IL-38 receptor was expressed on the cell surface of both CD4(+) and CD19(+) B lymphocytes. The splenic Th17 and DN T lymphocytes, the average mRNA level of epigenetically regulated gene expression of Th17 cells, and serum concentrations of IL-17 and IL-22 were significantly decreased upon the treatment of IL-38 (all p <0.05). The in vivo results suggest that IL-38 can ameliorate skin inflammation and nephritis in SLE mice probably via suppressing the formation of inflammatory cytokines such as IL-17 and IL-22, and pathogenic DN T cells. These findings may provide a biochemical basis for further investigation of the therapeutic mechanisms of IL-38 for the treatment of autoimmune-mediated inflammation. (C) 2016 Elsevier GmbH. All rights reserved.