TNFs

TNFs, or tumor necrosis factors, are cytokines that belong to the tumor necrosis factor (TNF) superfamily and play key roles in inflammation, immunity, cell survival, and apoptosis. The two best characterized members are TNF-α and TNF-β (lymphotoxin-α). TNF-α is produced mainly by macrophages and T cells in response to infections or inflammatory stimuli; TNF-β is produced by lymphocytes and can act in concert with TNF-α. The TNF family also includes additional ligands such as lymphotoxin-β and TNF-related apoptosis-inducing ligand (TRAIL). These ligands interact with TNF receptors to transmit signals that regulate immune responses and tissue homeostasis.

The primary receptors for TNF ligands are TNFR1 (p55) and TNFR2 (p75). TNFR1 is widely expressed and can trigger both pro-survival and pro-apoptotic pathways, depending on the cellular context, while TNFR2 is mainly found on immune cells and often promotes cell activation and survival. Signaling downstream of TNF receptors commonly involves NF-κB and MAPK pathways, leading to the production of inflammatory mediators, as well as caspase-dependent cascades that can induce apoptosis under certain conditions.

Physiologically, TNFs contribute to host defense by coordinating inflammation, recruiting leukocytes, and promoting the clearance of pathogens. They also participate in fever and the acute phase response. Dysregulated TNF signaling is implicated in several autoimmune and inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and certain vasculitides.

Therapies targeting TNF signaling, such as monoclonal antibodies (infliximab, adalimumab) and soluble receptors (etanercept), are used to treat various inflammatory conditions. While effective, anti-TNF treatments carry risks, including infections and rare adverse effects, and are not suitable for all patients.