TNF and rheumatoid arthritis: FRβ-expressing macrophages were reported to have produced TNF-α and reactive oxygen species14 and to act as M1 macrophages in rheumatoid arthritis.30 However, it remains controversial whether FRβ expression reflects M1 function because FRβ macrophages are considered to be M2 macrophages in glioma16 and melanoma.31 The patterns of gene expression of M1/M2 macrophages vary in response to various environmental stimuli, and FRβ in atherosclerotic lesions is heterogeneous and does not precisely fit either M1 or M2 in vivo.