Effect of topical cimetidine rinse on gingival crevicular neutrophil leukocyte function

Background: Three coordinated mechanism-of-action clinical studies were conducted to examine the effects of topical cimetidine rinse on neutrophil function in the gingival crevice. Methods: The first study was a randomized, double-blind, placebo-controlled, 28-day experimental gingivitis study involving 21 healthy adults, in which subjects rinsed twice a day with placebo or 0.5% cimetidine rinses. At baseline and days 14, 21, and 28, neutrophils were harvested from prespecified gingival sulcular sites, purified, stained, and examined by trifluorochrome phagocytosis and killing microassay. The second and third studies were placebo-controlled, 9-week, three-period (each of 3 weeks' duration), longitudinal studies involving seven and nine adults with moderate periodontitis, respectively. Subjects rinsed twice a day during periods 1 and 3 with placebo and during period 2 with 0.5% cimetidine. At baseline and weekly intervals, neutrophils were harvested from prespecified periodontal pockets, purified, stained, and examined by trifluorochrome phagocytosis and killing microassay in the second study. In the third study, neutrophils were examined spectrophotometrically for superoxide production and in a luminol-enhanced chemiluminescence assay. Results: In the first study, the mean number of phagocytosing neutrophils was statistically significantly increased (P = 0.016) in the cimetidine group (31.1 cells/subject) versus the placebo group (13.7 cells/subject) at day 28. In addition, a statistically significant increase (P = 0.036) in bacterial killing was observed in the cimetidine rinse group; in the cimetidine group, 63.4% of bacteria in the neutrophils were killed compared to 46.2% in the placebo group. Additional data from the other two studies support these findings. Conclusion: Collectively, these studies provide evidence that topical 0.5% cimetidine oral rinse enhances the antibacterial function of crevicular neutrophils.