IL-38: A new factor in rheumatoid arthritis

Area of Science:

• Immunology
• Cytokine Biology
• Rheumatology

Background:

• Interleukin-38 (IL-38) is a member of the IL-1 family, with prior research suggesting it inhibits IL-17 production.
• The precise role of IL-38 in inflammation, whether pro-inflammatory or anti-inflammatory, remains incompletely understood.

Purpose of the Study:

• To investigate the biological function of IL-38 in the context of inflammation and autoimmune diseases.
• To determine if IL-38 plays a role in the pathogenesis of rheumatoid arthritis (RA).

Main Methods:

• Generation of anti-human IL-38 monoclonal antibodies for immunohistochemical staining and ELISA.
• In vitro cleavage assays of human recombinant IL-38 protein.
• Analysis of IL-38 expression in synovial tissues from RA patients.
• Utilizing a collagen-induced arthritis mouse model with IL-38 gene-deficient mice.

Main Results:

• Overexpression of IL-38 cDNA yielded a soluble form of the protein.
• Immunohistochemistry revealed strong IL-38 protein expression in synovial tissues of RA patients.
• IL-38 gene-deficient mice exhibited increased disease severity in an autoantibody-induced arthritis model.
• These mice also showed elevated IL-1β and IL-6 gene expression in joints compared to controls.

Conclusions:

• IL-38 functions as an inhibitor of autoantibody-induced arthritis pathogenesis in mice.
• IL-38 may be implicated in the development or progression of rheumatoid arthritis in humans.