Signaling molecules of immune system are cytokines that may either stimulate or suppress the responses of various cells involved in host immune mechanisms and Tumor Necrosis Factor (TNF) is one of the leading members of the group of cytokines. TNF-α from activated macrophages and LT-α/TNF-Β from T cells have now become representatives of a distinctive superfamily of cytokine ligands (TNF ligand superfamily) along with their corresponding receptors (TNF receptor superfamily); altogether constituting the TNF Superfamily. These are highly conserved proteins, found in all mammals having important ligand members which interact with the either of the two receptors, TNFR1 and TNFR2, that initiate varied signaling cascades leading to diverse cellular responses. It has been established that the appropriate regulation of TNF ligand and receptor interactions and functions are crucial for the proper immune system activity. Excessive production of various TNF cytokines has been attributed with the development of an array of autoimmune as well as inflammatory conditions. TNF cytokines help to reduce mortality due to cardiovascular diseases. Therapeutic TNF blockers include:monoclonal antibodies to TNF (Infliximab and Adalumimab) and TNF receptor fusion proteins (Etanercept and Lenercept) and are effective against rheumatoid arthritis; ankylosing spondylitis; psoriasis and asthma. Preclinical studies conducted in murine models and the pivotal role played by the TNF superfamily in cytokine mediator system will make it easier for researchers as well as scientists to develop novel drugs in near future. This review has covered all these aspects concerning TNF as mediator of inflammatory diseases and its therapeutic targeting.
Kuldeep Dhama, Shyma K. Latheef, Hari Abdul Samad, Sandip Chakraborty, Ruchi Tiwari, Amit Kumar and Anu Rahal, 2013. Tumor Necrosis Factor as Mediator of Inflammatory Diseases and its Therapeutic Targeting: A Review. Journal of Medical Sciences, 13: 226-235.