While the ability of IFN-α to induce acute inflammatory responses and mood changes highlights its potential as an immune model of depression for future studies in healthy humans, we find no evidence of a putative neuroinflammatory response, and we unequivocally demonstrate that brain TSPO-PET signal measurement is confounded by the inflammation-induced changes in [11C]PBR28 free ligand in the plasma. The gene discussed is TSPO; the disease is major depressive disorder.