Neutralizing Interleukin (IL)-6

The proposed study aims to establish the feasibility and safety of subcutaneous tocilizumab, a monoclonal antibody (mAb) against interleukin (IL)-6 receptor, in adults with Major Depressive Disorder (MDD) and evidence of peripheral immune activation. IL-6 is a pro-inflammatory cytokine implicated in the pathophysiology of depression. The investigators hypothesize that neutralizing peripheral immune signaling via IL-6 receptor blockade with tocilizumab will improve neural and behavioral measures of reward processing. This is an open-label, proof-of concept, trial in which up to N=20 adults with MDD meeting a specific immune enrichment criterion will receive open-label tocilizumab over 8 weeks. A healthy control (HC) group (N=20) will undergo baseline neuroimaging and blood-based biomarker assessment without receiving the study drug to aid interpretation of findings. Blood-based immune markers and brain MRI scans (including task-based reward activation and resting-state functional connectivity) will be assessed at baseline for all participants and again post treatment for the MDD group.