Crohn\'s Disease: Promising New Findings

Crohn's Disease: Promising New Findings About Its Molecular Basis

Like it or not, the human digestive system requires bacteria to operate. But if these friendly bacteria penetrate the wall of the intestine the bacteria can become harmful rather than helpful. "This is why a thin, continuous layer of interconnected cells, called an epithelium, lines the intestinal surface creating a barrier that prevents bacteria from crossing that border"("Researchers Identify Molecular Basis of Inflammatory Bowel Disease," 2007, European Molecular Biology). Until recently, the mechanisms that control the epithelium were unknown. Now scientists have discovered what they call "NF-kB," a signaling molecule that helps cells cope with stress by reducing inflammation in the intestinal epithelium "("Researchers Identify Molecular Basis of Inflammatory Bowel Disease," 2007, European Molecular Biology). Scientists created a mouse that does not express NEMO, a protein needed to activate NF-kB, in intestinal epithelial cells. "As a result, these mice developed severe chronic intestinal inflammation very similar to the human disease known as Crohn's" ("Researchers Identify Molecular Basis of Inflammatory Bowel Disease," 2007, European Molecular Biology).

Crohn's disease impairs the lives of more than four million people worldwide ("Researchers Identify Molecular Basis of Inflammatory Bowel Disease," 2007, European Molecular Biology). It is a chronic inflammatory disorder that can produce abdominal pain, diarrhea and weight loss. Traditional treatment therapies for Crohn's disease involve antibiotics, anti-inflammatory drugs, steroids, and surgery (Feller 2001:1). Crohn's appears to run in families. Previous research indicated that it was caused by a combination of genetic and environmental causes, the degree to which appeared uncertain. For example, two Swedish studies suggested that the risk of contracting Crohn's disease might be increased in individuals whose mothers had contracted measles during pregnancy, but subsequent research discounted the data collection involved in the studies, and found no correlation or causation in the proposed connection (Metcalf 1998:1).

The most promising research prior to the study of NB-kB research suggested that the standard treatment of first giving Crohn's patients traditional corticosteroids and then turning to newer types of anti-inflammatory drugs should be reversed. Researchers randomly assigned 65 Crohn's patients to get a combination of anti-inflammatory drugs and then steroids while a group of 64 other Crohn's patients received the conventional treatment of steroids first, followed later by the same two anti-inflammatory drugs used in the other trial. After 6 months, 60% of those who initially received infliximab and azathioprine, the anti-inflammatory drugs, were entirely free of Crohn's disease symptoms, while only 36% of those getting steroids were asymptomatic, a heartening result given the severe side effects of steroids in comparison to these other drugs (such as weight gain and osteoporosis). The study supports the findings of the recent NF-kB research given that infliximab neutralizes an inflammation-causing protein called tumor necrosis factor alpha. This protein regulates "a common inflammation pathway that just happens to be important in Crohn's disease," suggesting that a specific, targeted molecular approach to treatment may be more helpful for Crohn's patients than steroids (Seppa 2008)

Future drugs, however, could directly address the problems regarding NF-kB, rather than simply treating the symptoms of inflammation. "NF-kB acts as a survival signal for cells. Without the molecule cells are much more likely to die and this is what happened in the intestines of... [the] mice; individual epithelial cells died disrupting the gut lining. Through these gaps bacteria could penetrate the intestinal wall. Right behind the gut epithelium lie cells of the intestinal immune system, the biggest immune system of our body. It detects the invading bacteria and generates a strong immune response to fight off the invaders. In the process of combating the bacteria, the immune cells secrete a cocktail of signals that bring about the symptoms of inflammation...Inflammatory signals also reach the epithelial cells that due to the lack of NF-kB are very sensitive to them and die. The death of more epithelial cells creates bigger gaps in the gut lining so that more bacteria enter. The result is a constant immune response leading to chronic inflammation" ("Researchers Identify Molecular Basis of Inflammatory Bowel Disease," 2007, European Molecular Biology).