Macrophages and lymphocyte subpopulations in nifedepine- and cyclosporin A-associated human gingival overgrowth

Background: Nifedipine and cyclosporin A (CsA) induce gingival overgrowth. Both drugs have immunomodulating effects. It has been suggested that altere d immune response is associated with drug-induced gingival overgrowth. In t his study, we evaluated whether there were differences in macrophages and l ymphocyte subpopulations in human nifedipine- and CsA-associated gingival o vergrowth as compared with those in normal gingiva. Methods: Biopsy samples of overgrown gingiva were obtained from 9 nifedipin e-treated cardiac outpatients, 13 CsA-treated renal transplant recipients i ncluding 9 patients who were also receiving nifedipine, and 30 healthy cont rol individuals undergoing dental treatment. Serial 5 mum thick cryostat se ctions were stained with mAbs for CD20 (B-pan), CD68 (macrophages), CD4 (T- helper/inducer), and CD8 (T-cytotoxic/suppressor) using an avidin-biotin-ho rseradish peroxidase complex method. Numbers of mAb-labeled and all nucleat ed cells were determined in 3 areas: the connective tissue beneath the sulc ular epithelium, the middle connective tissue, and the connective tissue be neath the oral epithelium. Distributions of each type of cell were expresse d as percentages of mAb-labeled cells in relation to total number of nuclea ted cells in a counting zone. Significances of differences between groups w ere tested by means of the Kruskal-Wallis test, and between pairs of result s by means of the Mann-Whitney U-test. Results: The proportion of CD8-labeled cells was significantly higher in co nnective tissue beneath the sulcular epithelium in the nifedipine group tha n in the controls (P = 0.014). In both medicated groups, the proportions of CD68-labeled cells were higher in all counting zones than in the controls, but statistically significantly only in the nifedipine group in the connec tive tissue beneath the oral epithelium (P = 0.008). No intergroup differen ces were found with respect to CD4- and CD20-labeled cells. The CD4/CD8 rat io was significantly lower in connective tissue beneath the sulcular epithe lium in the nifedipine group than in the controls (P = 0.013). Conclusion: The results support the idea that immune response may be altere d in drug-induced gingival overgrowth.