 The molecular mechanisms underlying induction of epithelial defensins remain largely unexplored. Pattern-recognition receptors 16 likely play a critical role in this process, as has been shown in CD-14-mediated induction of Beta-defensins by bacterial lipopolysaccharide 17. Whole heat-killed bacteria and fungi induce human Beta-defensins-2 in human keratinocytes, but the molecular basis of this response is not understood 11. Inflammatory cytokines such as tumor necrosis factor Alpha TNF and IL-10 also induces Beta-defensins 18, 19. Because pharmacological induction of defensins at epithelial barriers may have therapeutic utility, a search for novel molecules that could induce production of epithelial defensin, assessed by using cell-based assays, have long been underway. It has recently been observed that L-isoleucine and its analogues are highly specific Beta-defensin inducers in epithelial cells 20. It has also been observed that when isoleucine is administered to animals chicken, the gut flora shifts to the probiotic species, it stimulates paneth cells to secrete antimicrobial peptides in human intestinal tissue, and it causes a shift in gut flora leading to an increased numbers of Lactobacilli. Manuscript, Ashida T M Zasloff et al in treatment of patients with Crohns disease. 