TNF and arthritic joint disease: The relevance between macrophages and p21 in RA has been highlighted by several studies, including the studies by Trakala et al. that reported increased IL-1β and TNF-α expression in p21−/− macrophages in vitro46, and by Mavers et al., who found remarkably increased macrophage infiltration in the ankles of a p21−/− arthritis mouse model and significantly elevated IL-1α serum levels31.