Co-culture of the biologic agent CTLA4-Ig with SMs from RA patients has also been shown to significantly downregulate the expression of cytokines IL-6, TNF-α, and IL-1β, indicating that CTLA4-Ig has an indirect and direct anti-inflammatory effect on primary monocultures of RA SMs (48). Here, CTLA4 is linked to rheumatoid arthritis.