CHANGES IN CREVICULAR FLUID LEVELS OF INTERLEUKIN-1-BETA, LEUKOTRIENE-B4, PROSTAGLANDIN-E2, THROMBOXANE-B2 AND TUMOR-NECROSIS-FACTOR-ALPHA IN EXPERIMENTAL GINGIVITIS IN HUMANS

We conducted a study to determine the sequence of cytokine and lipid mediator activation within the periodontium during the development of experimental gingivitis in humans. Crevicular fluid samples were collected from 7 previously cleaned, healthy patients at baseline, 1, 2, 3 and 4 weeks following the cessation of all oral hygiene measures. Gingival and plaque scores were taken at each visit to follow the development of gingivitis and plaque retention. Crevicular fluid samples were assayed in quadruplicate for prostaglandin E2 (PGE2), thromboxane B2 (TxB2), leukotriene B4, interleukin-1beta (IL-1beta) and tumour necrosis factor alpha (TNFalpha) by RIAs or ELISAs, maintaining site pairing to examine temporal changes. Redness scores (expressed as mean percentage of sites with redness present) increased almost linearly from a baseline value of zero to approximately 40% at 1 week, 59% at 2 weeks, 83% at 3 weeks and 100% at 4 weeks. The mean % of sites with bleeding on probing increased gradually from zero at baseline to 5% at 3 weeks and then rose abruptly to 25% at 4 weeks. CF-PGE2 and CF-TxB2 levels remained fairly stable at baseline levels for the first 3 weeks then rose sharply by 2.5- and 2-fold, respectively, at 4 weeks. CF-LTB4 levels increased 2-fold by 1 week and 4-fold by 4 weeks. The CF levels of IL-1beta increased abruptly from mean baseline values of 16.5 +/- 9.3 ng/ml to 131 +/- 76.0 ng/ml at 1 week and remained at this level for the duration of the experiment. CF-TNFalpha levels were non-detectable throughout the experiment (i.e. < 2 ng/ml). These data suggest that LTB4 and IL-1beta are involved in the earliest stages of gingivitis and that increases in the cyclooxygenase products PGE2 and TxB2 occur later and are associated with an increase in bleeding scores.