Figure 2. Anti-TNF drug infliximab activates NF-κB c-Rel and p65 subunits, and triggers secretion of the pro-inflammatory cytokines IL-1β, IL-6, IL-8 and IL-12 in PBMCs isolated from TRAPS patients.

(1) The mAb anti-TNF drug infliximab triggers pro-inflammatory cytokine secretion due to failure to internalize or shed cell surface TNFR1, (2) resulting in TNF-stimulated NF-κB activation through the canonical pathway or ligand-independent TNFR1 signalling. This in turn results in nuclear translocation of p65 and c-Rel subunits of NF-κB, c-Rel-mediated reinforcement of the inhibition of apoptosis, and (3) transcriptional activation of cell survival pathways, increased pro-inflammatory cytokine secretion and the onset of TRAPS.