Antibiotic or Anti-inflammatory Agent? The Double-Edged Sword of Tetracyclines

The tetracyclines are broad-spectrum bacteriostatic antibiotics which interfere with the protein synthesis of bacteria at the ribosomal level. More recently the nonantibiotic properties of tetracyclines have attracted increasing interest. Since the initial observations that tetracyclines inhibit collagenases, extensive number of studies have shown that tetracyclines have effects on inflammation, proteolysis, angiogenesis, apoptosis, and bone metabolism. The mechanism of their action is complex and not completely understood. It includes inhibition of free radical formation and cytokine production, interference with protein synthesis, and modulation of matrix metalloproteinase activity. Chemically modified tetracyclines (CMTs) are tetracycline derivates which lack the antibiotic activity of tetracyclines but possess anti-inflammatory properties. The therapeutic effects of tetracyclines and its analogues have been studied in various inflammatory diseases. Encouraging results have been obtained in the treatment of rheumatoid arthritis (RA) and based on those results minocycline is currently used in the treatment of selected RA patients. Doxycycline has been approved for the treatment of adult periodontal diseases and rosacea. The role of tetracyclines has been studied also in cardiovascular diseases and neuroprotection but their true potential in these diseases remains to be determined. In this review the nonantibiotic properties of tetracycline and its analogues will be examined and their potential for clinical applications in inflammatory diseases will be discussed.