Tumour Necrosis Factor (TNF)
A pro-inflammatory cytokine produced primarily by macrophages that plays central roles in inflammation, immune regulation, and programmed cell death. TNF is a major therapeutic target in autoimmune diseases. While anti-TNF drugs are typically antibodies, understanding TNF biology provides context for peptide-based immune modulation.
Technical Context
TNF-α (233 amino acid transmembrane protein, cleaved to 157 amino acid soluble form by TACE/ADAM17) signals through TNFR1 (ubiquitous expression, mediating inflammation and apoptosis) and TNFR2 (restricted to immune and endothelial cells, mediating cell survival and proliferation). TNF-α is produced primarily by activated macrophages and T cells. Effects: NF-κB activation (pro-inflammatory gene transcription), MAPK activation (cytokine production), and caspase activation (apoptosis in some contexts). TNF-α is a central mediator of: septic shock (vasodilation, capillary leak, organ failure), rheumatoid arthritis (synovial inflammation and joint destruction), inflammatory bowel disease, and psoriasis. Anti-TNF therapies (infliximab, adalimumab, etanercept — antibodies and receptor fusion proteins) are blockbuster drugs. While these are protein/antibody therapeutics rather than peptides, understanding TNF biology contextualises the inflammatory pathways that peptide immunomodulators (corticotropin, cyclosporine) affect.