IL6 and rheumatoid arthritis: Besides, participants in 4 of total 5 studies analyzing the association of IL-6 -174 variants with circulating IL-6 level were healthy controls, suggesting that the negative causality is more reflective of condition in normal controls.[19,39–41] Considering the functional pleiotropy of IL-6 (both pro- and antiinflammatory)[9] and the absence of long-term cohort epidemiological study, we cannot deny the potential protective role of IL-6 for RA risk in health controls.