Journal of Medical Sciences1682-44741812-5727Asian Network for Scientific Information10.3923/jms.2013.226.235DhamaKuldeep LatheefShyma K.SamadHari AbdulChakrabortySandip TiwariRuchi KumarAmit RahalAnu 42013134Signaling 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.]]>Al-Lamki, R.S., J. Wang, P. Vandenabeele, J.A. Bradley and S. Thiru et al.,20051-and TNFR2- mediated signaling pathways in human kidney are cell type-specific and differentially contribute to renal injury.]]>1916371645Al-Lamki, R.S., T.J. Sadler, J. Wang, M.J. Reid and A.Y. Warren et al.,2010177943954Arnett, H.A., J. Mason, M. Marino, K. Suzuki, G.K. Matsushima and J.P. Ting,2001411161122Ashkenazi, A. and V.M. Dixit,199828113051308Bach, E.A., M. Aguet and R.D. Schreiber,199715563591Balkwill, F.,200625409416Behrendt, A.K. and G. Hansen,20101331927Bradley, J.R.,2008214149160Castro, J.E., J.A. Listman, B.A. Jacobson, Y. Wang and P.A. Lopez et al.,19965617627Chang, J.H., Y.S. Ryang, T. Morio, S.K. Lee and E.J. Chang,2004Trichomonas vaginalis inhibits proinflammatory cytokine production in macrophages by suppressing NF-kappaB activation.]]>18177185Chaudhari, U., P. Romano, L.D. Mulcahy, L.T. Dooley, D.G. Baker and A.B. Gottlieb,200135718421847Chauhan, R.S. and K. Dhama,20082008Clark, J., P. Vagenas, M. Panesar and A.P. Cope,200564iv70iv76Croft, M.,20033609620Croft, M.,200314265273Croft, M.,20099271285Croft, M.,2010285778Croft, M., W. Duan, H. Choi, S. Eun, S. Madireddi and A. Mehta,201233144153Darnell Jr., J.E.,199733216301633Deb, R., S. Chakraborty, B.M. Veeregowda, A.K. Verma, R. Tiwari and K. Dhama,20132013Dhama, K., R. Rathore, R.S. Chauhan and T. Simmi,20051115Dhama, K., R.S. Chauhan and L. Singhal,20051125Dhama, K. and R.S. Chauhan,20082008pp: 1733Dhama, K., M. Mahendran, R.S. Chauhan and S. Tomar,2008107989Dhama, K., A. Hansa and Anjaneya,20112011Dhama, K., S. Chakraborty, Mahima, M.Y. Wani and A.K. Verma et al.,201316101111 Dolff, S., D. Quandt, B. Wilde, T. Feldkamp and F. Hua et al.,20102010Esposito, E. and S. Cuzzocrea,20091631523167Fang, L., B. Adkins, V. Deyev and E.R. Podack,200820510371048Fousteri, G., A. Dave, B. Morin, S. Omid, M. Croft and M.G. Von Herrath,201136210220Francois, R.J., L. Neure, J. Sieper and J. Braun,200665713720Gabay, C. and I. Kushner,1999340448454Galuppo, M., G. Nocentini, E. Mazzon, S. Ronchetti and E. Esposito et al.,201116211861201Geiler, J., M. Buch and M.F. McDermott,20111731413154Gillett, A., M. Marta, T. Jin, J. Tuncel and P. Leclerc et al.,2010185442450Gottlieb, A.B., R. Evans, S. Li, L.M.T. Dooley and C.A. Guzzo et al.,200451534542Haritunians, T., K.D. Taylor, S.R. Targan, M.D.M. Dubinsky and M.D.A. Ippoliti et al.,20101618301840Hotamisligil, G.S., N.S. Shargill and B.M. Spiegelman, 19932598791 Jung, J.H., Y.S. Chae, J.H. Moon, B.W. Kang and J.G. Kim et al.,2010136685694Khare, S.D., I. Sarosi, X. Xia, S. McCabe and K. Miner et al.,20009733703375Kodama, S., M. Davis and D.L. Faustmana,20056218501862Lange, U., J. Teichmann and H. Stracke,20005507511Lee, B.H., S.Y. Park, K.B. Kang, R.W. Park and I.S. Kim,200229712181224Leung, L. and C.M. Cahill,20102010Lievens, D., A. Zernecke, T. Seijkens, O. Soehnlein and L. Beckers et al.,201011643174327Locksley, R.M., N. Killeen and M.J. Lenardo,2001104487501Mahima, A. Rahal, R. Deb, S.K. Latheef and H.A. Samad et al.,201215754774Mark, K.S., W.J. Trickler and D.W. Miller,200129710511058Meylan, F., Y.J. Song, I. Fuss, S. Villarreal and E. Kahle et al.,20114172185Mukhopadhyay, S., J.R. Hoidal and T.K. Mukherjee,20062006Nawashiro, H., D. Martin and J.M. Hallenbeck,1997778265271Nguyen, Q.T., S.A. Ju, S.M. Park, S.C. Lee, H. Yagita, I.H. Lee and B.S. Kim,20097739323938Nolte, M.A., R.W. van Olffen, K.P.J.M. van Gisbergen and R.A.W. van Lier,2009229216231Oflazoglu, E., I.S. Grewal and H. Gerber,20092009pp: 174-185pp: 174-185Peters, A.L., L.L. Stunz and G.A. Bishop,200921293300Pfeffer, K., T. Matsuyama, T.M. Kundig, A. Wakeham and K. Kishihara et al.,1993L. monocytogenes infection.]]>73457467Rothe, J., W. Lesslauer, H. Lotscher, Y. Lang and P. Koebel et al.,1993Listeria monocytogenes.]]>364798802Sands, B.E., F.H. Anderson, C.N. Bernstein, W.Y. Chey and B.G. Feagan et al.,2004350876885Shu, H.B., W.H. Hu and H. Johnson,199965680683Siddiqui, S., V. Mistry, C. Doe, S. Stinson, M. Foster and C. Brightling,2010137797804Sumi, T., W. Ishida, A. Ojima, M. Kajisako, T. Sakanishi, H. Yagita and A. Fukushima,20081199196Sun, X., S. Somada, K. Shibata, H. Muta and H. Yamada et al.,2008134447458Sun, X., H. Yamada, K. Shibata, H. Muta and K. Tani et al.,201018576717680Szlosarek, P.W. and F.R. Balkwill,20034565573Tansey, M.G. and D.E. Szymkowski,20091410821088Taylor, L., M. Bachler, I. Duncan, S. Keen and R. Fallon et al.,2002In vitro and in vivo activities of OX40 (CD134)-IgG fusion protein isoforms with different levels of immune-effector functions.]]>72522529Thompson, A.E., S.W. Rieder and J.E. Pope,20116314791485Tizard, I.R.,20042004pp: 133-144pp: 133-144Tracey, D., L. Klareskog, E.H. Sasso, J.G. Salfeld and P.P. Tak,2008117244279Tracey, K.J. and A. Cerami,199445491503Tremelling, M., C. Berzuini, D. Massey, F. Bredin and C. Price et al.,200814733737Tyring, S., K.B. Gordon, Y. Poulin, R.G. Langley, A.B. Gottlieb, M. Dunn and A. Jahreis,2007143719726Watkins, L.R., S.F. Maier and L.E. Goehler,199563289302Wolfe, F. and K. Michaud,2004116305311Yang, J., Y. Chu, X. Yang, D. Gao and L. Zhu et al.,20096014721483Zhang, J., X. Wang, H. Fahmi, S. Wojcik and J. Fikes et al.,200918353505357Zhang, Z., W. Zhong, D. Hinrichs, X. Wu and A. Weinberg et al.,201017729122920Zimmerer, J.M., P.H. Horne, L.A. Fiessinger, M.G. Fisher, T.A. Pham, S.L. Saklayen and G.L. Bumgardner,20129411031110