The vast and growing array of cytokines is the subject of intense research
for their potential to ameliorate a range of diseases that extends from aut
oimmune disorders to cancer and beyond. Among the cytokines. tumor necrosis
factor-alpha (TNF-alpha) has proven to he a key ligand in triggering many
intracellular processes, both physiological and pathological. Understanding
its role in rheumatoid arthritis and Crohn's disease has produced effectiv
e new therapeutic agents, and there is reason to expect greater success as
research proceeds. New synthetic macromolecules are effectively interfering
with TNF and other ligands at and before the cellular membrane interface.
This article reviews current knowledge of the molecular mechanics of TNF an
d the therapeutic inhibition of TNF action. Unraveling these processes has
led to many insights into cytokine physiology and pathology.