Tetracyclines inhibit tissue collagenases. Effects of ingested low-dose and local delivery systems.

In a series of experiments, Golub et al. demonstrated that tetracyclines, but not other antibiotics, can inhibit mammalian collagenases and proposed that this property could be useful in treating diseases, such as periodontal disease (but also included certain medical conditions, e.g., corneal ulcers) characterized by excessive collagen degradation {JPeriodont Res 1983, 1984 and 1985; Experientia 1984; Cornea 1984). One effect was the dramatic reduction of tissue collagenase activity within the gingival crevicular fluid (GCF) of periodontal pockets after administering a standard regimen of a tetracycline (e.g., 200 mg minocycline or 1000 mg tetracycline/day). The preliminary studies described below determined the effect of (1) low-dose (LD; 40-80 mg/day) orally administered minocycline on GCF collagenase activity and on the subgingival microflora (Exp. I), and (2) tetracyclineloaded monolithic fibers (TF) on collagenase activity in vitro (Exp. II). In Exp. I, GCF collagenase activity was reduced by 45 to 80% 2 weeks after initiating LD minocycline therapy, an effect that lasted for at least several weeks after stopping drug treatment. No consistent change in the relative proportions of G(+), G(-) and motile subgingival microorganisms was detected as a result of LD treatment suggesting that the reduction in GCF collagenase activity was a direct inhibition of the enzyme by the drug. In Exp. II, 3- and 6mm lengths of TF in vitro established tetracycline concentrations in 250 μl of 132 μg/ml, from 3-mm lengths, and 265 μg/ml, from 6-mm lengths, after an 18-hour incubation. Although these concentrations were slightly lower than those established in the GCF of individual TF-treated periodontal pockets in vivo (Goodson et al. 1983, J Periodontol), the released tetracycline from 3- and 6-mm TFs inhibited rat polymorphonuclear leukocyte collagenase activity in vitro by 21 % and 45%, respectively (bacterial collagenase activity was also inhibited in vitro). These results indicate that TF placed into individual periodontal pockets could maintain a level of tetracycline in GCF that would effectively inhibit tissue (and perhaps also bacterial) collagenases at the lesion site.