Anti-TNF therapies in rheumatoid arthritis, Crohn's disease, sepsis, and myelodysplastic syndromes.
An attempt has been made in this article to summarize the state-of-the-art clinical experience with the use of anti-TNF therapies in four diseased states with special emphasis on myelodysplastic syndromes. Given the central role of TNF-alpha in initiating and perpetuating the chronic damage produced in the diseased organs by controlling a cascade of pro-inflammatory cytokines, as well as its acute role in sepsis, theoretically speaking, neutralization of this peptide was a natural therapeutic choice. Results of the initial clinical trials appear encouraging and sometimes dramatic in their efficacy. The mechanism of response however, is interesting in that even when TNF-alpha is directly targeted by a monoclonal antibody, the resulting benefits can frequently not be attributed to TNF suppression alone. Rather, it appears that a more general effect on the T-lymphocytes is also contributing to the responses being seen. This raises the new possibility of combining anti-cytokine and anti-T-cell strategies to treat at least the more chronic diseases such as Crohn's disease and myelodysplastic syndromes. Continued clinical trials testing these strategies are clearly warranted.
Raza
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Rush Cancer Institute, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3515, USA.araza@rush.edu
D001172:Arthritis, Rheumatoid / Q000628:therapy*; D003424:Crohn Disease / Q000628:therapy*; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D010431:Pentoxifylline / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D018805:Sepsis / Q000628:therapy*; D013792:Thalidomide / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D000068800:Etanercept; D010431:Pentoxifylline