Reflux oesophagitis due to immune reaction, not acute acid burn

Contrary to current thinking, a condition called gastro oesophageal reflux disease (GORD) might not develop as a direct result of acidic digestive juices burning the oesophagus, University of Texas Southwestern Medical Center researchers have found in an animal study.

Rather, gastro-oesophageal reflux spurs the oesophageal cells to release chemicals called cytokines, which attract inflammatory cells to the oesophagus. It is those inflammatory cells, drawn to the oesophagus by cytokines, that cause the oesophageal damage that is characteristic of GORD. The condition is manifested by symptoms such as heartburn and chest pain.

"Currently, we treat GORD by giving medications to prevent the stomach from making acid," said Dr Rhonda Souza, associate professor of internal medicine at UT Southwestern and lead author of the study appearing the November issue of Gastroenterology. "But if GORD is really an immune-mediated injury, maybe we should create medications that would prevent these cytokines from attracting inflammatory cells to the oesophagus and starting the injury in the first place."

In the study, researchers created GORD in rats by connecting the duodenum to the oesophagus. This operation allows stomach acid and bile to enter the oesophagus. Researchers were surprised to learn that oesophagitis didn’t develop for a number of weeks after the operation.

"That doesn’t make sense if GORD is really the result of an acid burn, as we all were taught in medical school," said Dr Stuart Spechler, professor of internal medicine at UT Southwestern and senior author of the study. "Chemical injuries develop immediately. If you spill battery acid on your hand, you don’t have to wait a month to see the damage."

About 40 percent of Americans suffer symptoms of GORD at some point, and 20 percent on a weekly basis, Dr Souza said. Over the long term, GORD could eventually lead to oesophageal cancer.

Previous studies had shown that if an animal oesophagus is perfused with highly concentrated acid, oesophageal damage develops quickly. In humans, however, the large majority of reflux episodes do not contain such highly concentrated acid, Dr Souza said.

"In animal models of reflux oesophagitis designed to mimic the human disease, researchers hadn’t looked at the early events in the development of oesophageal injury," Dr Souza noted. "Most of those investigators have been interested in the long-term consequences of GORD, and we found virtually no published data about what happens later that induces gastrooesophageal reflux."

Dr Souza, who is also a staff physician at the Dallas Veterans Affairs Medical Center and part of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern, and Dr Spechler, chief of gastroenterology at the Dallas VA, said the method they used to produce GORD in rats is a reasonable representation of how GORD develops in humans – acidic digestive juices from the stomach surge into the oesophagus.

Soon after the operation, they expected to see the death of surface cells of the oesophagus, and they expected to see the injury progress later to the deeper layers. Instead, they found the opposite. Three days after the surgery, there was no damage to surface cells, but the researchers did find inflammatory cells in the deeper layers of the oesophagus. Those inflammatory cells didn’t rise to the surface layer until three weeks after the initial acid exposure.

The next step for researchers is to conduct additional studies in humans.

(Source: University of Texast Southwestern: Gastroenterology: November 2009)