The modulation of CD14 expression by antifolates that we now report supports the anti-inflammatory role of MTX in RA patients and leads us to suggest that MTX-treated RA patients would exhibit lower levels of sCD14 and mCD14 in myeloid cells, lower responsiveness to TLR4-dependent damage-associated molecular patterns (DAMPs), and a lower proinflammatory profile. The gene discussed is TLR4; the disease is rheumatoid arthritis.