TNF-α (Tumour Necrosis Factor alpha)

Tumour Necrosis Factor alpha is a pleiotropic pro-inflammatory cytokine produced predominantly by macrophages and monocytes in response to infection or tissue damage, signalling through two receptors — TNFR1 (widely expressed, mediates inflammation and apoptosis) and TNFR2 (expressed mainly on immune and endothelial cells, implicated in cell survival and immunoregulation). At the cellular level, TNF-α activates NF-κB and MAPK pathways, driving expression of adhesion molecules, other cytokines, and acute-phase proteins. Chronically elevated TNF-α is a recognised component of inflammaging, contributing to insulin resistance, muscle wasting (cachexia/sarcopenia), and neuroinflammation. Anti-TNF biologics such as etanercept, infliximab, and adalimumab are established treatments for rheumatoid arthritis and inflammatory bowel disease, and their potential relevance to age-related inflammatory conditions is an active area of translational interest.