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Oxidation, bactericidal action & inflammation: where do antibiotics fit in?
How can low dose antibiotics given on alternating days be a high enough dose to be effective? The answer lies in part with the process of oxidation, in part with the action of neutrophils and in part with the organism (mycoplasma).
The Process of Oxidation
The metabolism of aerobic bacteria (like our own metabolism) requires oxygen... All organisms normally produce tiny amounts of a free radical of oxygen, superoxide. Superoxide is very toxic, and aerobic cells are believed to survive only because they possess the enzyme super-oxide dismutase (SOD), which scavenges the superoxide radical. Most anerobes (like mycoplasmas) lack SOD and cannot tolerate the presence of free oxygen.3,4
Hydrogen peroxide is the end product of superoxide breakdown by SOD. This compound is also very toxic and will kill cells if it is not destroyed. Aerobic bacteria accomplish this by producing the enzyme, catalase, but anerobic bacteria, like mycoplasmas, are unable to synthesize catalase. Oxygen is doubly dangerous to them because they cannot destroy superoxide or hydrogen peroxide.3
In a healthy cell, there is a balance between superoxide production and superoxide savenging. The superoxide SOD is a protective therapeutic agent. "It is produced by a number of bacteria and tissue cells to inactivate the toxic effects of superoxide, a natural product of oxidation and a highly reactive anion that causes inflammation."1
Dr. Brown found superoxide in the absence of SOD inhibits the growth of some strains of mycoplasma such as M. hominis, where growth is completely obliterated in 6 hrs. while in the presence of SOD growth is unaffected. A commer-cial preparation of SOD was also found effective against M. arthritidis over a 48 hr. period.2,4
Another agent eliciting SOD activity is tetracycline...Although this drug family has both antimicrobial and anti-inflammatory properties, in vitro studies cannot provide the total picture because of the more complex environment of the human host. The response to treatment depends on both the mycoplasma's and the host's response to the drug.2
The Action of Neutrophils
"The neutrophil is programmed for overkill; because so much is at risk if it fails to carry our its mission...The anti-biotics...in (its) arsenal are of the broadest possible spectrum...Therefore, an inflammatory locus becomes littered with casualties. Host tissue cells succumb to the oxidant attack, along with microbes and the neutrophils themselves. Infected tissues display the cardinal signs of inflammation (redness, heat, swelling, pain, and loss of function) not necessarily as a result of the invading microbe, but largely due to the war waged by the attacking neutrophils and the unavoidable damage to host tissues."1
"Thus, in the case of bactericidal action and inflammation we see paradoxical actions of superoxide. We also see the logic of the concept of balance. In the case of autoimmune diseases and allergies the war may be waged at a perceived, but nonexistent or non-threatening enemy. The result of this overproduction of superoxide is damage to the organism. In the case of any immune compromise there may be underproduction of superoxide, and again the result is damage to the organism. The balance may be remarkably delicate."2
If an imbalance of SOD exists in the neutrophil, the cell may be rendered less able to kill microbes.2
Mycoplasma's Part
Because the mycoplasma is a slow-growing organism, it does not need high, continuous doses of antibiotic to control or eliminate it as is the case with bacteria. Its parasitic nature makes it more difficult to eliminate in a human host, necessitating a long-term treatment. It is not unusual for antibiotic therapy to require 3-5 years to achieve a remission, especially in patients with long-term disease and who are immunosuppressed from past DMARDs.
Prescribing the tetracycline antibiotic to be used on alternating days gives the body a breather from the potential oxidation damage to host tissues while still being effective against the slow-growing mycoplasma - thus eventually leading to improvement in disease manifestations as well as in the long-term course of the disease.
References:
1 JM McCord, Superoxide Radical: Controversies, Contradictions, and Paradoxes, Soc for Exper Biol & Med, 1995, pgs. 112-117.
2 T McP Brown, JS Bailey, I I Iden, HW Clark, Anti-mycoplasma Approach to the Mechanism and the Control of Rheumatoid Disease, Inflam Diseases and Copper, Humana Press, 1982, pg 391-407.
3 Wesley A. Volk, Ch 5, 'Bacterial Nutrition', Basic Microbiology, 7th ed., 1992, pg. 69-79.
4 HW Clark, T McP Brown, JS Bailey, I I Iden, Superoxide as an agent of toxic potential for mycoplasma, (abstract) Annual Meeting of the Am Soc for Microbiol, 1985, G10.
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