Mycoplasmas & Rheumatic Disease

by Harold W. Clark, Ph.D.

Dr. Clark, microbiologist, worked with Dr. Thomas McP. Brown for 35 years. Together they explored the part myco-plasma plays in rheumatic disease, studied the unique properties of this tiniest free-living microbe and its amazing adaptability to the human body.

MYCOPLASMAS & RHEUMATIC DISEASE:

Treatment

Why is intermittent dosing important, especially with a drug (tetracycline) that is multiple acting and not just antimicrobial?

* With intermittent dosing there is less chance of causing resistant strains. There is the precedent of other therapies (gold, methotrexate) where the intermittent dose was found to be less toxic and thus more effective.

* Intermittent dosing also allows recovery of the host tissues from antioxidants, immunosuppressants, and protein synthesis inhibitor effects.

* It is more effective to chip away with intermittent antibiotics for long periods with eventual removal of the infectious agent than overwhelm the tissues with drug toxicity.

* A drug's actions on the host tissues (toxicity) is more critical than its effect on a benign microbial agent.

* Nucleophilic and lipophilic agents are localized, limiting systemic spread.

* Chelated tetracyclines fixed in bone and other low metabolic tissue (cartilage and collagen) provide a pool, replenished by intermittent dosage. Excessive long-term dosage could permanently damage organ functions and negate any benefits. Gold salts are a good example. The MIRA patients managed to survive 48 weeks of high daily doses protected by NSAIDs. Intermittent dosing allows the patient to tolerate the medication for years, if necessary.

* Antibiotic effectiveness is dependent upon the tissue infected. Different IV or oral dosages may be required to clear the fatty synovium tissue than the genital tract, for example.

Pathogenicity

* Because of the complex pathogenicity, even with specific genetic coding, a pathogen becomes a set of conditions that regulates the host-parasite or saprophytic interaction.

* A pathogenic substance that causes a delayed or persistent abnormal host response in one set of conditions may be nonpathogenic in another set.

* Some strains of human mycoplasma and ureaplasma strains (M pneumoniae, M hominis) are known pathogens for respiratory and genitourinary tract symptoms. However, in tissue cell cultures, M. hominis (and other strains) were found to coexist unrecognized as noncytopathogenic saprophytes.

* Another form of mycoplasma pathogenicity is their interaction with the host as autoantigens and the selective adhesion and conformation of specific cell membrane antigens.¹ The cell-bound immune complexes have been cited as pathogens for rheumatic diseases.²

At what point or clinical level does a host response become pathogenic?

* The pathogen may have been transmitted in utero and lay dormant until the host cells become receptive.

* The disease or the host response depends on the pathogen's portal of entry as well as the receptive tissues.

* The introduction of mycoplasmas or other foreign antigens could elicit pathogenic host responses such as white blood cell activation, resulting in inflammation and tissue destruction.

* The attachment of viable mycoplasmas to blood and lymph vessels could be responsible for impaired circulation with the resulting pathogenic symptoms. The restricted circulation would be similar to mycoplasma's pathogenic production of agalactia in goats or citroplasma's restriction of capillary fluid in plant wilting diseases.

Characteristics of the organism

* We are treating both extracellular and/or intracellular agents. Having low cytopathogenicity, mycoplasmas can remain attached to (or in) tissue culture cells for weeks or months without killing the cells as long as the cells continue to produce nutrients.

* Mycoplasmas have limited synthetic abilities, live off dying or dead cells - requiring and utilizing cellular fragments (peptides, nucleotides, lipids and cholesterol) for growth.

What part does cholesterol play?

* Mycoplasmas growing in a high cholesterol media will incorporate higher cholesterol composition especially in their lipid membrane and thus may adhere to tissues with elevated lipids as well as mucoproteins found in synovium and vascular tissues. There they can either initiate an inflammatory reaction and/or interfere with cellular functions such as plaque deposition.

* Human mycoplasma strains grown in elevated cholesterol media had variable tetracycline sensitivity - some improved and some worsened. I would suspect that persons with high blood cholesterol would be at greater risk for mycoplasma reactivity including their deposition/ adherence in various tissues.

How can mycoplasma be eliminated?

* Mycoplasmas can divide by hexagonal budding. The tissue cells can continue to grow, divide and die while the myco-plasma cells (with multiple antigens) will continue to grow and divide in the absence of growth inhibiting antibodies and antibiotics. Mycoplasmas are primarily pro-sacrophytic, living off (dead) tissue cell fragments (peptides, nucleotides, lipids & cholesterol) requiring digested tissue for cell-free growth.

* Mycoplasmas in animals and humans can remain untouched (resistant) by antibiotics and antiserum (vaccines) and noncultured as long as they remain cellular bound. Only when the mycoplasmas are released (cellular death) can they be isolated and respond to antibiotics and antisera.

* Stopping or slowing mycoplasma growth with antibiotics limits the pro- duction of new antigens while making old accumulated antigen available for a Herxheimer reaction with excess IgG antibody. The reaction is not the same in all patients.

What about the role of steroids?

* As a precursor, excessive available cholesterol may enhance the production of the hormonal steroids. Details of the role estrogen plays in rheumatoid diseases are primarily limited to its role in bone metabolism, such as osteo- porosis. Like corticosteroids, estrogens and anabolic steroids can be helpful or harmful.

* Some doctors advocate using a mixed hormonal therapy for RA. The danger in this is again not targeting the infectious agent and in getting the right combination of dosage for each different patient.

* Steroid changes can also lead to a post menopausal flare in some and a stabilizing effect in others.

* During pregnancy, the hormonal immunosuppression of foreign fetal antigen may also suppress the RA.

* While RA improves in most pregnancies, not all RA pregnancies improve before a postpartum flare. Most RA patients experience post partum flares.

WARNING: The symptoms and their causes are highly individualized making it difficult to identify any cause and effect relationship. Although estrogen undoubtedly plays a role in RA incidence, the infectious agent(s) and the host's susceptibility are the primary cause. As reported, I found women to have positive mycoplasma serology 4 times that found in males, which supports but does not prove the infectious cause theory.

References:

1 HW Clark, Am J Primatology, 24: 235-243.

2 The Role of Immune Complexes in Disease, World Health Org., Tech Report Series 606, 1977.

3 HW Clark, Sedimentation Counting and Morphology of Mycoplasma, J Bacteriol, 1965, 90:5, 1373-86.

4 HW Clark, JS Bailey, TMcP Brown, Medium- dependent Properties of Mycoplasmas, Diag Microbiol Infect Dis, 1985; 3: 283-294.

5 HW Clark, MR Coker-Vann, JS Bailey, TMcP Brown, Detection of mycoplasmal antigens in immunocomplexes from rheumatoid arthritis synovial fluids, Ann of Allergy, 1988; 60:5, 394-398.

6 HW Clark, personal communications, 1996, 1997,1998.

* Pathogenicity is a complex set of conditions that regulate the host-parasite relationship.

* Excessive long-term dosage can permanently damage organ functions. Small doses can stimulate the antibiotic effect; large doses can suffocate. Titrate the dose based on host response and tolerance.

* When it is intracellular, the mycopalsma cannot be cultured nor will it respond to antibiotics or antisera.

Only when the mycoplasma is released (cellular death of host cell) can it be isolated and respond to antibiotics.

* Dosage varies with the location of the mycoplasma. ie, clearing the fatty synovium tissue may require higher dosages than clearing the genital tract.