Aging considerations of cytokines (IL-18, IL-36α, IL-37, and IL-38) associated with rheumatoid arthritis

Abstract

ABSTRACT The pro-inflammatory cytokines IL-18 and IL-36α and the anti-inflammatory cytokines IL-37 and IL-38 are proposed to have a pathophysiological role in rheumatoid arthritis (RA). However, this role has not been well investigated in relation to aging. In this study, serum IL-18, IL-36α, IL-37, and IL-38 levels were examined in 100 RA patients who were classified as young adults (<40 years) and elderly (>60 years). A similar classification was applied to 100 healthy controls. Serum IL-18, IL-36α, and IL-38 levels were significantly elevated in all RA patients compared to controls. When comparing young adult patients to elderly patients, only IL-18 showed significantly elevated levels in elderly patients. IL-18, IL-36α, and IL-38 showed excellent performance in differentiating between young adult patients and young adult controls, whereas in elderly patients, only IL-37 retained this performance. IL-18, IL-36α, and IL-38 were associated with an increased risk of RA in young adults, whereas in the elderly, only IL-37 was associated with an increased risk of RA. In conclusion, aging is an important factor proposed to influence the association pattern of IL-18, IL-36α, IL-37, and IL-38 in RA. These findings may reshape our understanding of the role of cytokines in the pathophysiology of RA.