Antifibrotic therapy in scleroderma: extracellular or intracellular targeting of activated fibroblasts?

Curr Rheumatol Rep. 2004 Apr;6(2):164-70. doi: 10.1007/s11926-004-0062-8.


Therapeutic anticytokine approaches have revolutionized the treatment of chronic inflammatory diseases, and targeting of transforming growth factor-beta (TGF-beta), a key factor in the pathogenesis of fibrosis, is undergoing evaluation for scleroderma. Several considerations dictate a cautious approach to anti-TGF-beta interventions. These include the possibility of multiple cytokines having overlapping roles in the pathogenesis of fibrosis and concerns that, in light of its numerous homeostatic functions, blocking TGF-beta may have serious adverse consequences. Furthermore, as autonomously activated cells, scleroderma fibroblasts may be unresponsive to blockade of TGF-beta signaling. This article reviews the experimental evidence underlying these concerns, and indicates rational approaches to addressing and overcoming them.

Publication types

  • Review

MeSH terms

  • Fibroblasts / physiology*
  • Humans
  • Lymphotoxin-alpha / antagonists & inhibitors*
  • Scleroderma, Systemic / physiopathology*
  • Scleroderma, Systemic / therapy*
  • Signal Transduction / physiology*


  • Lymphotoxin-alpha