TNFalpha blockade in human diseases : mechanisms and future directions

Tumor necrosis factor-alpha (TNFalpha) antagonists have shown remarkable efficacy in a variety of immune-mediated inflammatory diseases (IMIDs). Therapeutic scope and limitations of these agents are reviewed in a recently published article in the Journal. In spite of their therapeutic popularity, li...

Ausführliche Beschreibung

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 126(2008), 2 vom: 01. Feb., Seite 121-36
1. Verfasser: Wong, Maida (VerfasserIn)
Weitere Verfasser: Ziring, David, Korin, Yael, Desai, Sheetal, Kim, Sungjin, Lin, Jan, Gjertson, David, Braun, Jonathan, Reed, Elaine, Singh, Ram Raj
Format: Aufsatz
Sprache:English
Veröffentlicht: 2008
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review Anti-Inflammatory Agents, Non-Steroidal Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Antirheumatic Agents Cytokines Immunoglobulin G mehr... Receptors, Tumor Necrosis Factor Tumor Necrosis Factor-alpha Infliximab B72HH48FLU Adalimumab FYS6T7F842 Etanercept OP401G7OJC
LEADER 01000caa a22002652 4500
001 NLM17419742X
003 DE-627
005 20250208181853.0
007 tu
008 231223s2008 xx ||||| 00| ||eng c
028 5 2 |a pubmed25n0581.xml 
035 |a (DE-627)NLM17419742X 
035 |a (NLM)17916444 
040 |a DE-627  |b ger  |c DE-627  |e rakwb 
041 |a eng 
100 1 |a Wong, Maida  |e verfasserin  |4 aut 
245 1 0 |a TNFalpha blockade in human diseases  |b mechanisms and future directions 
264 1 |c 2008 
336 |a Text  |b txt  |2 rdacontent 
337 |a ohne Hilfsmittel zu benutzen  |b n  |2 rdamedia 
338 |a Band  |b nc  |2 rdacarrier 
500 |a Date Completed 28.02.2008 
500 |a Date Revised 12.03.2024 
500 |a published: Print-Electronic 
500 |a Citation Status MEDLINE 
520 |a Tumor necrosis factor-alpha (TNFalpha) antagonists have shown remarkable efficacy in a variety of immune-mediated inflammatory diseases (IMIDs). Therapeutic scope and limitations of these agents are reviewed in a recently published article in the Journal. In spite of their therapeutic popularity, little is known about their modes of action in vivo and factors that limit their scope of therapeutic use. Intriguingly, while all TNFalpha antagonists including blocking antibodies and soluble receptors are effective in certain IMIDs, only anti-TNFalpha antibodies are effective in other IMIDs. Early efforts at understanding how TNFalpha antagonists act in IMIDs centered on their ability to neutralize soluble TNFalpha or to block TNF receptors from binding to their ligands. Subsequent studies suggested a role of complement-mediated lysis or antibody-dependent cell cytotoxicity in their therapeutic effects. More recent models postulate that TNFalpha blockers may act by affecting intracellular signaling, with the end result being a hastened cell cycle arrest, apoptosis, suppression of cytokine production, or improved Treg cell function. TNFalpha antagonists can also modulate the functions of myofibroblasts and osteoclasts, which might explain how TNFalpha antagonists reduce tissue damage in chronic IMIDs. Focusing on the human therapeutic experience, this analytical review will review the biology of mechanisms of action, the limiting factors contributing to disease restriction in therapeutic efficacy, and the mechanism and frequency of treatment-limiting adverse responses of TNFalpha antagonists. It is hoped that the overview will address the needs of clinicians to decide on optimal use, spur clinical innovation, and incite translational researchers to set priorities for in vivo human investigations 
650 4 |a Journal Article 
650 4 |a Research Support, N.I.H., Extramural 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Review 
650 7 |a Anti-Inflammatory Agents, Non-Steroidal  |2 NLM 
650 7 |a Antibodies, Monoclonal  |2 NLM 
650 7 |a Antibodies, Monoclonal, Humanized  |2 NLM 
650 7 |a Antirheumatic Agents  |2 NLM 
650 7 |a Cytokines  |2 NLM 
650 7 |a Immunoglobulin G  |2 NLM 
650 7 |a Receptors, Tumor Necrosis Factor  |2 NLM 
650 7 |a Tumor Necrosis Factor-alpha  |2 NLM 
650 7 |a Infliximab  |2 NLM 
650 7 |a B72HH48FLU  |2 NLM 
650 7 |a Adalimumab  |2 NLM 
650 7 |a FYS6T7F842  |2 NLM 
650 7 |a Etanercept  |2 NLM 
650 7 |a OP401G7OJC  |2 NLM 
700 1 |a Ziring, David  |e verfasserin  |4 aut 
700 1 |a Korin, Yael  |e verfasserin  |4 aut 
700 1 |a Desai, Sheetal  |e verfasserin  |4 aut 
700 1 |a Kim, Sungjin  |e verfasserin  |4 aut 
700 1 |a Lin, Jan  |e verfasserin  |4 aut 
700 1 |a Gjertson, David  |e verfasserin  |4 aut 
700 1 |a Braun, Jonathan  |e verfasserin  |4 aut 
700 1 |a Reed, Elaine  |e verfasserin  |4 aut 
700 1 |a Singh, Ram Raj  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Clinical immunology (Orlando, Fla.)  |d 1999  |g 126(2008), 2 vom: 01. Feb., Seite 121-36  |w (DE-627)NLM098196855  |x 1521-6616  |7 nnns 
773 1 8 |g volume:126  |g year:2008  |g number:2  |g day:01  |g month:02  |g pages:121-36 
912 |a GBV_USEFLAG_A 
912 |a SYSFLAG_A 
912 |a GBV_NLM 
912 |a GBV_ILN_11 
912 |a GBV_ILN_24 
912 |a GBV_ILN_350 
951 |a AR 
952 |d 126  |j 2008  |e 2  |b 01  |c 02  |h 121-36