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The Multiple Properties of Tetracyclines
While antibiotic therapy is based on the concept of an infectious etiology, tetracyclines have many properties.
Anti-inflammatory Action
Of obvious benefit would be the anti-inflammatory effect of tetracyclines. Since many forms of arthritis are inflammatory in nature, it is a standard part of therapy to prescribe some form of NSAID to control this symptom.
Collagenase Inhibitor
Tetracyclines inhibit certain enzymes such as collagenase, the host-derived enzyme responsible for the breakdown of collagen which is released during the inflammatory process. In a 1990 NYS Dental Journal1, L. M. Golub concluded tetracycline treatment was useful in the treatment of periodontal disease but also "for medical diseases that are characterized by excessive collagen and connective tissue destruction."1
Robert Greenwald, M.D. of Long Island Jewish Hospital, found minocycline reduced excessive collagenase activity in diseased joints of patients with severe rheumatoid arthritis.2 These findings were confirmed in 1990 by David E. Trentham, M.D. in two animal models.3
Normalizes Bone-forming Cell Activity
Tokyo microscopist, Sasaki, found tetracycline normalized the morphology and activity of osteoblasts, bone forming cells, in diabetics.4
Potent Chelating Agents
HW Clark, PhD. noted "tetracyclines are potent chelating agents, and as such have been found to act as: anti-inflammatory (electron scavengers), immunosuppressive, anti-metalo-enzymes (anti-collagenase & anti-lysosomes), as well as antibiotic. Consequently the parenteral (IV, IM) or oral (between meals) administration could have a pronounced effect on their chelated state (Cu, Fe, Zn, Ca, etc) with variable dissociation constants that would determine the reactivity."5
Dr. Clark continues, "Bioassays for tetracycline levels in fluids and tissues measure the bacterial antibiotic activity and do not account for the variety of other activities that would be dependent upon the dissociation constant of the chelated divalent metals. Thus when tetracyclines enter the blood or tissues as the sodium salt, it may exchange with the iron, copper, zinc, etc. resulting in greater or lesser tissue affinity and activity.
Extra Benefit of IV over Oral
Consequently, the IV therapy would produce more constant activity than the highly variable (between meals) oral route even though antibiotic levels were similar."5
When considering cytotoxicity of tetracycline, Dr. Clark learned during his years with Dr. Thomas McP Brown, that tissue cell cultures will survive pulse treatment of tetracyclines but not constant exposure, even at lower doses.5
Low Cytotoxicity
In RA, there apparently is no need to keep on top of a virulent cyto-pathogenic agent with high daily doses that could be replaced with less toxic and resistant, intermittent therapy, controlling both the host's reactions and the foreign antigens.5
Anti-microbial Activity
Although it remains technically unproven that the anti-microbial property of the tetracyclines may be what is responsible for the sometimes dramatic response to treatment in previously unresponsive patients, it must be noted that there is an abundance of journal research on the topic. Among the candidates mentioned in The Arthritis Foundation's Primer on the Rheumatic Diseases are: "Candidate viruses: T cell lymphotropic virus Type-1 and other retroviruses, Epstein-Barr virus and other herpes viruses, rubella virus and parvoviruses. Candidate bacteria include mycoplasma, mycobacteria, and various enteric organisms."6 The article author, Ronald L. Wilder, M.D., notes that "failure to culture an organism from a joint does not exclude its involvement in RA, because it has become increasingly clear that dead whole bacteria, cell walls, toxins and other components of a micro-organism have the capacity to induce chronic inflammatory joint disease."6
A letter to the editor in the March, 1997 issue of Arthritis & Rheumatism reported the detection by PCR assay, of M fermentans in synovial specimens of various conditions, including rheumatoid arthritis.7,8
The articles in support of a micro-organism as a cause or trigger are too numerous to list here. Our search goes back as far as 1939 and finds the research coming from all over the world from a large number of researchers. Although still considered unproven, we feel there is sufficient evidence in the current literature to at least present a strong suspicion that an organism responsive to tetracycline antibiotics is most probably involved, and would justify treating these diseases as if they are an infection, with antibiotics as the drugs of choice.
References:
1 Lorne M Golub DMD, Reduction with Tetracyclines of Excessive Collagen Degradation in Periodontal and Other Diseases, NYS Dental Journal, May 1990, 24-26.
2 Robert Greenwald, et al, Tetracyclines Inhibit Human Synovial Collagenase in vivo and in Vitro, J of Rheum, 1987; 14:28-32.
3 DE Trentham, Novel Therapies, Curr Opin Rhu, 1990; 2, 506-509.
4 T Sasaki, et al, Insulin-deficient Diabetes Impairs Osteoblast and Periodontal Ligament Fibroblast Metabolism, but Does Not Affect Ameloblasts and Odontoblasts: Response to Tetracycline(s) Administration, J Biol Buccale, 1990; 18: 215-226.
5 HW Clark, Tetracyclines - Multiple Action Drugs, Mycoplasma Research Inst Newsletter, July 1990, 1.
6 RL Wilder, Rheumatoid Arthritis, Epidemiology, Pathology and Pathogenesis, Prim on Rheum Dis, 10th ed, 1993, 86-89.
7 T Schaeverbeke, T Gilroy, C Bebear, J Dehais, D Taylor-robinson, Mycoplasma fermentans in joints of patients with rheumatoid arthritis and other joint disorders, Lancet, 1996; 347: 1418.
8 T Scheverbeke, C Bebar, et al, Reactive or Septic Arthritis? Comment on the article by Li et al, Arth & Rheum, 1997; 40:3, 592-592.
Mycoplasmas cause acute and chronic arthritis in many animals and should be considered as candidates for causing human joint disease. M. fermentans seems to be associated with some of the inflammatory arthritis diseases, including rheumatoid arhtritis.
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