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*Mycoplasma infections in Rheumatoid Arthritis patients

The History Of The Search For Cause And Cure

In the 1930's, a bacterial cause for rheumatoid arthritis was investigated but the research was short-lived except for distinct cases of acute infectious or septic arthritis. In 1939, the first real lead regarding an infectious cause for rheumatoid arthritis arose when mycoplasma, an atypical viral-like bacteria, was isolated from the exudate and tissue of rheumatic patients.

Investigators had already shown that mycoplasmas cause arthritis in mice, rats, chickens, goats, and cows. They had found mycoplasmas in the genitourinary tracts of humans too, especially females.

In 1949 at the International Congress on Rheumatic Diseases the possible relationship between mycoplasmas and joint disease was reported. After obtaining one of the first National Institutes of Health (NIH) research grants in 1950, Thomas McPherson Brown, M.D. and colleagues at the arthritis research unit reported the following year that the rheumatoid disease mechanism was more of an immunologic reaction of antigen and antibody (with mycoplasma as the suspected antigen) rather than the infectious and transmissible type.

In 1955, the research unit reported that mycoplasmas, unlike bacteria and viruses could live in tissue cell cultures without destroying the tissue cells. To further support mycoplasmas as a causative agent/antigen, in 1964 a high incidence of mycoplasma antibodies in the blood of rheumatoid arthritis patients and lupus patients was found, indicating current or previous infection. Also recognized was a 4:1 higher incidence of mycoplasma antibodies in females suggesting a correlation with the higher incidences of rheumatoid arthritis in females.

Effect of MALP-2, a lipopeptide from Mycoplasma fermentans, on bone resorption in vitro.

Piec G, Mirkovitch J, Palacio S, Muhlradt PF, Felix R.

Department of Clinical Research, Bone Biology, University of Bern, CH-3010 Bern, Switzerland.

Mycoplasmas may be associated with rheumatoid arthritis in various animal hosts. In humans, mycoplasma arthritis has been recorded in association with hypogammaglobulinemia. Mycoplasma fermentans is one mycoplasma species considered to be involved in causing arthritis. To clarify which mycoplasmal compounds contribute to the inflammatory, bone-destructive processes in arthritis, we used a well-defined lipopeptide, 2-kDa macrophage-activating lipopeptide (MALP-2) from M. fermentans, as an example of a class of macrophage-activating compounds ubiquitous in mycoplasmas, to study its effects on bone resorption. MALP-2 stimulated osteoclast-mediated bone resorption in murine calvaria cultures, with a maximal effect at around 2 nM. Anti-inflammatory drugs inhibited MALP-2-mediated bone resorption by about 30%. This finding suggests that MALP-2 stimulates bone resorption partially by stimulating the formation of prostaglandins. Since interleukin-6 (IL-6) stimulates bone resorption, we investigated IL-6 production in cultured calvaria. MALP-2 stimulated the liberation of IL-6, while no tumor necrosis factor was detectable. Additionally, MALP-2 stimulated low levels of NO in calvaria cultures, an effect which was strongly increased in the presence of gamma interferon, causing an inhibition of bone resorption. MALP-2 stimulated the bone-resorbing activity of osteoclasts isolated from long bones of newborn rats and cultured on dentine slices without affecting their number. In bone marrow cultures, MALP-2 inhibited the formation of osteoclasts. It appears that MALP-2 has two opposing effects: it increases the bone resorption in bone tissue by stimulation of mature osteoclasts but inhibits the formation of new ones.

PMID: 10569738 [PubMed - indexed for MEDLINE]

Mycoplasma arthritis in man and mechanisms of its pathogenesis]

[Article in Russian]

Gorina LG, Vul'fovich IuV, Zil'fian AV, Rakovskaia IV, Pronin AV.

Possible etiologic contribution of mycoplasma to human rheumatoid arthritis (RA) is supported by their recovery from synovial fluid of RA patients, as well as Mycoplasma antigens and antibodies detection in the bloodstream. The detectability of free antigens of M. arthritidis (Ma) and M. fermentans (Mf) in the sera of patients was 22.4%, and that of antibodies against those, 52.7%. Considerable difference between the detectability of Mycoplasma antigens and antibodies can be attributed to the fact that the bulk of the antigens form part of immune complexes and cannot be detected by serologic tests. Mitogenic effect of arthritogenic Mycoplasma and their ability to produce a cytotoxic effect on various cells, including lymphocytes, appears to be a mechanism of immune process developing in association with human RA. A study of immunobiological properties of individual Ma and Mf cell components has shown that a protein factor translocated into the culture medium is responsible for mitogenic action. Ma cytotoxicity in respect of target cells is related to its cytoplasmatic membrane. Mf produces a factor, acting directly on rat lymphocytes; its synthesis is apparently taking place on the cell membrane.

PMID: 2773570 [PubMed - indexed for MEDLINE]

Why Arthritis?"

Throughout the years, the theories that focus on mycoplasma as the responsible infectious agent and on tetracycline as the antibiotic treatment of choice have been hampered by lack of adequate funding for more research and from politics. "Why Arthritis?" by Harold W. Clark, Ph.D., one of Brown's colleagues, assesses the rheumatoid diseases, decades of research, the search for a cure, and the frustration of researchers whose case for anti-mycoplasma therapy was overlooked for 40 years by the government and various arthritis organizations. Clark believes efforts were impeded because a safe, simple treatment threatens the medical establishment since patients would then require less medical intervention. 

Many physicians remain skeptical and still do not suggest antibiotic treatment to their patients. The Arthritis Foundation was seemingly unimpressed even after antibiotic therapy was deemed as safe and effective

Leaky-Gut Syndrome May Play A Role In Arthritis

Some researchers claim that leaky-gut syndrome, or increased intestinal permeability, is implicated in dozens of diseases. The syndrome is the result of the wall of the small intestine being damaged.

A healthy intestine allows only nutrients to pass into the bloodstream. When the intestine is damaged, larger molecules such as incompletely digested fats, proteins, starches, and even bacteria, also permeate the intestinal wall.

The larger molecules, recognized by the body as foreign substances, can trigger an immune response in other organs. Some researchers claim that healing a leaky gut with strict diet and nutritional supplements can help control conditions such as insomnia, obesity, bad breath, as well as a wide range of diseases including asthma, eczema, and arthritis. Many researchers agree that the intestinal tract is a key player in the immune system, but whether or not the gut is the root of so many problems is still the subject of hot debate.

The small intestine is a convoluted, 25-foot tube between the stomach and the large intestine. Its lining is comprised of millions of villi, or leaflike structures, which in turn are covered with millions of microvilli. The villi and microvilli harbor bacteria and yeast, which normally maintain a healthy balance and help to carry out the main function of the intestine which is to break down food into nutrients which the body can use, and to move along waste and harmful substances to the bowel. Most of the potentially dangerous material a human encounters is in food, therefore the gut's immune function is crucial. Researchers now estimate that more than two thirds of all immune activity occurs in the gut.

In some people the wall of the gut seems to have been breached. Researchers are unsure how these microscopic breaches occur but possible causes include food allergies, excessive amounts of aspirin or ibuprofen, certain antibiotics, excessive drinking, a compromised immune system, or a parasitic infection.

Leaky-gut syndrome is not a disease itself but is thought to play a role in other diseases. Allowing undigested food or bacteria into the bloodstream causes the immune system to react. As this occurs the body reacts in a number of ways such as rash, diarrhea, migraines, joint pain, and even psychological symptoms. These problems can add up to a disorder which has no obvious relation to the original cause.

Until a few decades ago, the theory was that unless a medical problem directly affected the gut, it worked normally. Now physicians know that trauma to other parts of the body causes the gut to react. One researcher, Leo Galland M.D., estimates that the syndrome plays a role in 70 percent of people with chronic fatigue syndrome, eight out of 10 aspirin or ibuprofen users, most alcoholics, and anyone who is hospitalized. Galland also believes that parasites that can lead to leaky-gut syndrome lurk in most municipal water systems.

One common prescription for leaky-gut syndrome is an elimination diet. A series of urine and blood tests is used to assess food allergies. Based on the results of the tests, whole categories of food such as dairy products or wheat products, are eliminated and added back over time as the patient is monitored for reactions. Strict elimination diets should be used only under close medical supervision, otherwise malnutrition can result.

The nutritional mainstay, fiber, may also play a role in healing problems of the gut. A National Institute of Health funded study from Louisiana State University indicated that rats who ate no fiber had abnormal intestinal linings. Other research shows that glutamine, a nonessential amino acid, also plays a role in maintaining the integrity of the intestinal wall.

To conclude from available research that leaky-gut syndrome is widespread, treatable, and the cause of all sorts of problems is a jump scientists and most doctors are unwilling to make. The gut and glutamine are definitely hot areas of current and ongoing research. It is recognized though that care and maintenance of the gut makes sense in any case.

REFERENCE:
Gut Reactions, by Wendy Marston, NEWSWEEK, 

*This  information is a collection of minerals and dietary supplements that are believed to be deficient in the body that promote the development of conditions that are unhealthy and take away from a natural healthy state. These statements have not been evaluated by the Food and Drug Administration. These products do not intended to diagnose, treat, cure, or prevent any disease. The information has been compiled from the information provided by those who have been helped from extensive research and experience. The information contained herein is not medical advice and is not intended to replace the advice or attention of health care professionals. Nor is this information intended to act as a "prescription" for treatment. These are ONLY suggestive guidelines for dietary supplements that may supplement the body's nutritional requirements to maintain optimum health. We advise  consulting your health care provider before beginning any new dietary supplement program.

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