Drug Discovery Opinion

Gastroesophageal reflux (GER), or acid reflux, which occurs when the lower esophageal sphincter opens spontaneously or doesn’t close properly, is experienced intermittently by most people. Gastroesophageal reflux disease (GERD) occurs when the amount of gastric juice that refluxes into the esophagus exceeds the normal limit and the esophageal mucosa is damaged, causing esophagitis. It has generally been thought that damage to the esophagus is the direct result of chemical burns by the acid in refluxed gastric juice but researchers at UT Southwestern Medical Center have now suggested that this may not be the case. The team created GERD in rats by connecting the duodenum to the esophagus, which allows stomach acid and bile to enter the esophagus, but were surprised to find that esophagitis didn’t develop for a number of weeks after the operation. If GERD is really caused by acid burns, the damage would be expected to appear much more quickly. In earlier studies, perfusion with highly concentrated acid did cause rapid damage to the esophagus, but early events in animal models designed to more closely resemble human GERD had not been investigated in detail.

In the present study, the researchers expected to see death of surface cells followed by injury to the deeper layers of the esophagus but found just the opposite. Reflux esophagitis started at postoperative day 3; at this stage there was no damage to surface epithelial cells, but lymphocytes had begun to infiltrate the submucosa and later progressed to the epithelial surface. Since damage to the deeper layers of the esophagus preceded surface erosions, the team suggest that it is infiltrating lymphocytes, rather than direct chemical burns, that cause the damage. Exposure of esophageal epithelial cells to acidified bile salts was shown to increase the secretion of cytokines interleukin-8 and interleukin-1β, and conditioned media from these cells was found to cause significant increases in the migration rates of T cells and neutrophils. Current treatments for GERD focus on reducing acid production by the stomach but the new study provides a more complex picture and suggests that treatments that modulate the immune response could also be of benefit.

The study is published in Gastroenterology.

Related posts:

1. GERD Linked to Changes in Oesophageal Microbiome The incidence of gastroesophageal reflux disease (GERD) has increased significantly in the United States since the 1970s. The chronic inflammation...
2. FDA Committee Recommends Approval of New Gout Treatment Although the first written descriptions of gout date back over 4000 years, it wasn’t until the mid nineteenth century that...
3. Opposing Roles for Brain Macrophages Systemic infection and inflammation lead to release of cytokines, such as IL-1, which activate the brain’s stress response mechanisms, producing...
4. Gut Flora Play Role in Immune Response It has been estimated that there are ten times as many bacterial cells as human cells in the body, with...

Related posts brought to you by Yet Another Related Posts Plugin.

 Email This Post

This entry was posted on Monday, November 30th, 2009 at 8:48 am and is filed under News. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.