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. Copyright 2000 Wiley-Liss, Inc.