Host modulation with tetracyclines and their chemically modified analogues.
Recent studies have suggested the use of drugs to modulate host response as a new approach in periodontal therapy. In this regard, the tetracycline antibiotics have been found to inhibit host-derived collagenases and other matrix metalloproteinases by a mechanism independent of the antimicrobial activity of these drugs; this effect may suppress connective tissue breakdown during periodontal disease and during a variety of medical disorders including (but not limited to) noninfected corneal ulcers, serious (sometimes life-threatening) skin-blistering diseases, rheumatoid arthritis and osteoarthritis, systemically--as well as locally--induced bone loss, and perhaps even tumor-induced angiogenesis. Two therapeutic strategies based on the host-modulating properties of tetracyclines are currently being developed: 1) the use of low-dose doxycycline (the most potent anticollagenase of commercially available tetracyclines) formulations, which do not appear to result in tetracycline side effects such as the emergence of antibiotic-resistant microorganisms; and 2) the production of a family of chemically modified tetracyclines that have lost their antimicrobial activity, but have retained their anticollagenase activity. A description of several of these compounds and a discussion of their efficacy in inhibiting collagenases in vitro and reducing tissue destruction in several animal models of periodontal and medical diseases is presented.
Golub
L M
LM
State University of New York at Stony Brook.
Suomalainen
K
K
Sorsa
T
T
D016301:Alveolar Bone Loss / Q000201:enzymology / Q000517:prevention & control; D000818:Animals; D003094:Collagen / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology; D005883:Gingival Crevicular Fluid / Q000201:enzymology; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010510:Periodontal Diseases / Q000188:drug therapy* / Q000201:enzymology*; D013754:Tetracyclines / Q000494:pharmacology / Q000627:therapeutic use*
D013754:Tetracyclines; D003094:Collagen; D008666:Metalloendopeptidases; D003012:Microbial Collagenase; D004318:Doxycycline