ABSTRACT
Tetracyclines are broad-spectrum antibiotics that act as such at the ribosomal level where they interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s when it was discovered that they were effective as a treatment for acne. More recently, biologic actions affecting inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism have been researched. The therapeutic effects of tetracycline and its analogues in various diseases have also been investigated. These include rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis, and autoimmune disorders such as rheumatoid arthritis and scleroderma. We review the nonantibiotic properties of tetracycline and its analogues and their potential for clinical application.
Subject(s)
Tetracyclines/pharmacology , Tetracyclines/therapeutic use , Acne Vulgaris/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Aortic Aneurysm, Abdominal/metabolism , Apoptosis/drug effects , Arthritis, Rheumatoid/drug therapy , Doxycycline/therapeutic use , Humans , Matrix Metalloproteinases/metabolism , Minocycline/pharmacology , Minocycline/therapeutic use , Neoplasms/drug therapy , Neovascularization, Physiologic/drug effects , Periodontitis/drug therapy , Rosacea/drug therapy , Sarcoma, Kaposi/drug therapy , Skin Diseases/drug therapy , Skin Diseases/physiopathology , Skin Diseases, Vesiculobullous/drug therapy , Tetracyclines/chemistryABSTRACT
The treatment of systemic sclerosis (scleroderma) is difficult and remains a great challenge to the clinician. Because the cause is unknown, therapies are directed to improve peripheral blood circulation with vasodilators and antiplatelet aggregation drugs, to prevent the synthesis and release of harmful cytokines with immunosuppressant drugs, and to inhibit or reduce fibrosis with agents that reduce collagen synthesis or enhance collagenase production. The purpose of this review is to critically analyze conventional and new treatments of systemic sclerosis and localized scleroderma. The therapeutic options discussed for the treatment of systemic sclerosis include the use of (1) vasodilators (calcium channel blockers [nifedipine], angiotensin-converting enzyme inhibitors [captopril, losartan potassium], and prostaglandins [iloprost, epoprostenol]), (2) immunosuppressant drugs (methotrexate, cyclosporine, cyclophosphamide, and extracorporeal photopheresis), and (3) antifibrotic agents (D-penicillamine, colchicine, interferon gamma, and relaxin). The treatment options reviewed for localized scleroderma include the use of corticosteroids, vitamin D analogues (calcitriol, calcipotriene), UV-A, and methotrexate. Preliminary reports on new therapies for systemic sclerosis are also considered. These include the use of minocycline, psoralen-UV-A, lung transplantation, autologous stem cell transplantation, etanercept, and thalidomide.
