DO INFILTRATING LEUKOCYTES CONTRIBUTE TO THE ADAPTATION OF HUMAN GASTRIC-MUCOSA TO CONTINUED ASPIRIN ADMINISTRATION

Background: Aspirin (ASA)-induced gastropathy decreases with continued ASA ingestion due to the development of gastric mucosal tolerance. Ho wever, the mechanism of the gastric mucosal adaptation to repeated ASA challenge is unknown. Methods. The aim of the present study was to de termine the density of leukocytes infiltrating the gastric mucosa in h ealthy subjects during prolonged treatment with ASA. In eight healthy volunteers ASA treatment (2 g/day) was continued for 14 days. Endoscop y was performed before medication, on the 3rd, 7th, and 14th day of AS A treatment, and on the 16th and 18th day (2 and 4 days after medicati on was stopped). Gastric damage was scored (Lanza score), and gastric biopsy specimens were taken from both the oxyntic and antral mucosa. R esults. ASA administration resulted in the development of hemorrhagic erosions, which were most severe on the 3rd day of the medication; lat er significant reduction of severity of the damage was observed. ASA a dministration caused an increased mucosal infiltration of leukocytes; leukocyte margination and adherence to endothelia were commonly observ ed in the gastric mucosa, particularly on the 3rd day of ASA treatment but not later on. Mast cell density increased significantly on the 3r d day of ASA treatment. Density of mast cells later decreased in the a ntral mucosa but continued to be significantly increased in the oxynti c mucosa up to the 14th day. There was a striking correspondence betwe en mast cell density and endoscopic score of the mucosal damage. Eosin ophil density increased significantly during ASA treatment and remaine d high even after medication was withdrawn. Conclusions: 1) Initial mu cosal damage by ASA is followed by gastric adaptation on continuous ex posure to this agent; 2) infiltrating leukocytes appear to contribute to the development of gastric mucosal adaptation to ASA; and 3) mast c ell density reflects the endoscopic score of gastric damage by ASA.