By Will Boggs, MD

NEW YORK (Reuters Health) – The presence of cyclooxygenase 2 (COX-2)-positive T cells in the small intestinal mucosa of patients with celiac disease suggests that COX-2 is involved in either mucosal restoration or disease induction, according to a report in the January issue of Gut.

COX-1 mediates the production of prostaglandins that play an important role in mucosal integrity, the authors explain, whereas COX-2 may have both pro- and anti-inflammatory functions.

Dr. Heikki Kainulainen from University of Tampere, Finland and colleagues investigated the expression of COX-2 in the small intestinal mucosa of 15 celiac disease patients and 15 nonceliac individuals.

Mucosal lesions consistent with celiac disease were seen in all 15 initial celiac disease biopsies, the authors report. After a mean of 10 months of treatment with a gluten free diet, 2 of 10 patients for whom biopsies were available showed completely normal mucosa, and the remaining 8 biopsies showed substantial mucosal recovery with only minor residual changes.

COX-2-positive cells populated the lamina propria beneath the basement membrane in all celiac lesions examined, the report indicates, but the density of such cells fell by half (p < 0.001) after a gluten free diet. Some COX-2-positive cells, however, persisted in the villi and crypts, though their distribution was similar to that seen in normal mucosa.

Subepithelial COX-2-positive cells predominated in areas where the epithelium blistered or detached from the underlying basement membrane, the researchers note, and the cells appeared to be T lymphocytes by immunostaining and electron microscopy.

The COX-2-positive cells in these two locations (within blisters or below the basement membrane) belonged to different populations of lymphocytes according to their immunoreactivity.

"Our results do not directly indicate whether COX-2 positive cells contribute to or ameliorate the inflammation," Dr. Kainulainen told Reuters Health. "Both aspects are possible and remain to be shown. However, we have 'a gut-feeling' that amelioration is probable."

"We have also some preliminary (unpublished) data showing that COX-2 positive cells are not always present in mucosal lesions of celiac children," Dr. Kainulainen said. "This indicates that COX-2 positive cells are not needed to produce the mucosal lesion, suggesting further that these COX-2 positive cells may have anti-inflammatory function or a place in mucosal restoration."

This theory, if correct, has potential implications for treatment with COX-2 inhibitors. "Celiac patients with rheumatoid arthritis and other diseases should potentially not be treated with COX-2 inhibitors," Dr. Kainulainen suggested, "since this might prevent the healing of mucosal lesions or even worsen the situation."