IL-1a is distinct from the other agonist member of the IL-1 family, IL-1b Although IL-la triggers the same IL-1 receptor and although many of the biological effects of IL-la are similar to those of IL-1b in humans IL-1a is predominantly an intracellular molecule. In fact, there is evidence that IL-lo has both intracellular functions as a precursor molecule due to a nuclear localization sequence. IL-1a as an unprocessed precursor is biologically as active as the processed form. IL-1a is also found consitutively in epithelial cells, whereas constitutive expression of IL-1b is rare. In many ways, IL-1a appears to be closer to the fibroblast growth factor family than the secreted IL-1b form. Therapeutic stratiegies for blocking IL-1b predominate over those for blocking IL-1a. Many humans have circulating neutralizing antibodies to IL-1a but not IL-1b.