THE LEVELS OF 3 BONE RESORPTIVE CYTOKINES, interleukin 1-alpha (IL-1-alpha), IL-1-beta, and tumor necrosis factor-alpha (TNF-alpha), were assessed in tissues from sites of periodontal disease. As determined by ELISA of tissue extracts, IL-1-beta and TNF-alpha were detected in all diseased sites, whereas IL-1-alpha was present in 8/22 sites. IL-1-beta was present in highest concentration (mean +/- SEM: 11,695 +/- 2,888 pg/ml; 672 pM), followed by TNF-alpha (434 +/- 135 pg/ml; 26 pM), and IL-1-alpha (342 +/- 160 pg/ml; 20 pM). The levels of all 3 mediators were significantly lower in clinically healthy tissues. There was a highly significant correlation between levels of IL-1-beta and TNF-alpha (r(s) = 0.61, P < 0.001), suggesting coordinated expression of these 2 mediators. The numbers of cells containing each mediator was also determined by indirect immunofluorescence on frozen tissue sections. Consistent with findings from tissue extracts, IL-1-beta-containing cells were present in approximately 5-fold higher numbers than TNF-alpha-containing cells, and 40-fold higher numbers than IL-1-alpha-containing cells. Taken together with previous findings, these results indicate that IL-1-beta is likely to be an important mediator in the pathogenesis of periodontal disease.