Multiple Sclerosis Research Focuses on Autoimmune Symptoms and Bacterium
March 5, 2010 posted by Denise Nichols · 5 Comments
Italian Researchers Discover A Possible Onset Mechanism For Multiple Sclerosis
A non-pathogenic bacterium is capable of triggering an autoimmune disease similar to multiple sclerosis in the mouse, the model animal which helps to explain how human diseases work. This is what a group of researchers from the Catholic University of Rome, led by Francesco Ria (Institute of General Pathology) and Giovanni Delogu (Institute of Microbiology), have explained for the first time in a recently published article on the Journal of Immunology.
Multiple sclerosis is caused by an inflammatory reaction provoked by the immune system, leading to disruption of the coating of the nerve fibres in the Central Nervous System.
“We do not know what causes multiple sclerosis”, explains Francesco Ria, immunologist of the Catholic University. “We know that there exists a genetic factor and an environmental factor, but we do not yet possess a satisfactory theory which can explain how exactly this environmental factor works”.
Currently, there are two competing theories in the field: according to a first hypothesis, a virus hides within the brain and what causes the disease is the immunologic antiviral reaction. On the other hand, the second hypothesis states that a viral or bacterial pathogen similar to specific molecules of the Central Nervous System causes an inflammation which provokes a reaction of the immune system. This reaction ends up destroying the brain cells. The latter is called the autoimmune hypothesis.
This is the hypothesis that the researchers coming from the Institutes of General Pathology, Microbiology and Anatomy of the Catholic University of Rome have been testing with their two-year long work. To demonstrate the viability of this idea, scientists have fooled the mouse immune system, modifying subtly a bacterium of the common family of mycobacteria (the same family to which also the bacterium causing tuberculosis belongs) to make it look like to myelin, the protein coating nerve cells. This modified mycobacterium is completely innocuous. As all external agents, though, it is capable to trigger the reaction of the T-cells of the immune systems. They intervene to destroy it. Since they are innocuous bacteria, although very common in the environment, and since they induce an immune reaction, they are the ideal bacteria scientists can use to study the environmental factor contributing, together with the genetic factor, to cause multiple sclerosis.
“Normally, T-cells cannot penetrate into the Central Nervous System”, adds Rea, “because the hematoencephalic barrier prevents them from doing so. But the bacterium modifies the characteristics of the T-cells and allows them to overcome the barrier. In 15 days the bacterium disappears completely from the body”.
Yet these T-cells can now enter into the brain. This way, they begin to attack the myelin of the nerve cells, and here is how the immune disease breaks out.
“We basically demonstrate – explains Rea – that in an animal model it is possible to be infected with something not carrying any disease, and later on develop a purely autoimmune disease”.
Yet there is another element in this complex research, sponsored by the Italian Association of Multiple Sclerosis (AISM). “Normally – clarifies Rea – to understand which diseases we have encountered, we measure the antibodies produced by that specific pathogen. But there is a whole world of infectious agents which do not induce the production of antibodies, as is the case in our research: mycobacteria and many other bacteria produce a very low and variable number of antibodies. It is thus very hard to establish whether a population has encountered that specific infectious agent. So, we demonstrate that those infectious agents which are more likely to produce an autoimmune reaction are just those which do not induce antibody production”.
Obviously, this is only the first step to better understand the way this very complex and devastating disease works. Ria and Delogu are not stopping here: “We want to try to understand the exact characteristics which this infectious agent should have”, they explain. “Might it truly be a good experimental model for multiple sclerosis? If we had prolonged the action of the bacteria, would we have favoured or hampered the development of the disease? And what about the myelin-like bacterium protein: where should it lie? On the surface, or inside? These are all questions – conclude the two researchers – which we will be trying to answer in the next years, in the hope to defeat this terrible illness. We could even imagine to develop a vaccine by which we could prevent the immune response associated to multiple sclerosis”.
Source:
Contact: Francesco Ria
fria@rm.unicatt.it
39-338-466-2776
Catholic University of Rome
Effects on rats of exposure to heat and vibration
H. Megel 1, H. Wozniak 1, L. Sun 1, E. Frazier 1, and H. C. Mason 1
1 Bioastronautics Section, Aero-Space Division, The Boeing Company, Seattle, Washington
Restrained adult male rats of the Sprague-Dawley strain were exposed for a 20-min duration to sublethal intensities of heat, vibration, and to the combination of heat and vibration. The incidence of mortality resulting from simultaneous exposure to both environmental stresses was significantly greater than would be predicted if these stresses were to act independently of each other. Hematocrit, hemoglobin, and serum glutamic-oxalacetic transaminase levels were significantly elevated immediately after vibration. Heat in combination with vibration increased these values although heat stress per se caused no change from control levels. Twenty-four hours after exposure to the combination of vibration and heat, hematocrit and hemoglobin levels returned to normal but the serum glutamic-oxalacetic transaminase levels were still significantly elevated. Significant increases in heart, kidney, and adrenal weights were observed immediately after exposure to the combination of environmental stresses. Possible modes of action are discusse
Nippon Hifuka Gakkai Zasshi. 1989 Feb;99(2):155-61.
[Two cases of scleroderma associated with vibration syndrome]
[Article in Japanese]
Matsumoto Y, Kawabe M, Yasue T, Yuguchi M, Yoshida I.
Case 1, a 49-year-old male who had been engaged in repair and reclamation of automobile tires, developed symptoms of vibration syndrome (Raynaud’s phenomenon, numbness of both hands, tinnitus and impaired hearing) after some 30 years’ use of a grinder and impact wrench. Two years thereafter, multiple sclerodermic lesions appeared over the trunk, upper extremities, and thighs; these disappeared about 2 years later. Histologically, hyperplasia and nodular swelling of collagen bundles were present in the dermis. An immunological study showed the serum to be positive for anti-centromere antibody, but no visceral lesions were demonstrable. This case corresponded to generalized morphea. Case 2, a 53-year-old male, developed symptoms of vibration syndrome (Raynaud’s phenomenon, numbness of both hands, impaired hearing and arthralgia) after 25 years’ use of a jack hammer in a quarry. Thereafter, sclerodermic changes of the forearms, lower legs, face and abdomen occurred with an associated sclerodactyly. Histological examination of involved skin revealed diffuse hyperplasia and homogenization of collagen bundles throughout the entire thickness of the dermis. These findings, together with serum positivity for anti-RNP antibody and dilation of the lower portion of the esophagus, led us to a diagnosis of progressive systemic sclerosis. We inferred that the vibration syndrome in the present cases might be related etiologically to these forms of scleroderma.
PMID: 2545958 [PubMed - indexed for MEDLINE]
Rats sure aren’t doing very well. Kinda like us Gulf war Vets. Hmmm, Imagine that.I always did like the Beach Boy’s song. Good Good Vibrations. I guess thats why orchestrator’s have the longest life span.
J Neuroinflammation. 2005 Nov 18;2:26.
Cytokine responses during chronic denervation.
Ruohonen S, Khademi M, Jagodic M, Taskinen HS, Olsson T, Röyttä M.
Department of Pathology, University of Turku, Kiinanmyllynkatu 10, 20520 Turku, Finland. saku.ruohonen@utu.fi
BACKGROUND: The aim of the present study was to examine inflammatory responses during Wallerian degeneration in rat peripheral nerve when the regrowth of axons was prevented by suturing. METHODS: Transected rat sciatic nerve was sutured and ligated to prevent reinnervation. The samples were collected from the left sciatic nerve distally and proximally from the point of transection. The endoneurium was separated from the surrounding epi- and perineurium to examine the expression of cytokines in both of these compartments. Macrophage invasion into endoneurium was investigated and Schwann cell proliferation was followed as well as the expression of cytokines IL-1beta, IL-10, IFN-gamma and TNF-alpha mRNA. The samples were collected from 1 day up to 5 weeks after the primary operation. RESULTS: At days 1 to 3 after injury in the epi-/perineurium of the proximal and distal stump, a marked expression of the pro-inflammatory cytokines TNF-alpha and IL-1beta and of the anti-inflammatory cytokine IL-10 was observed. Concurrently, numerous macrophages started to gather into the epineurium of both proximal and distal stumps. At day 7 the number of macrophages decreased in the perineurium and increased markedly in the endoneurium of both stumps. At this time point marked expression of TNF-alpha and IFN-gamma mRNA was observed in the endo- and epi-/perineurium of the proximal stump. At day 14 a marked increase in the expression of IL-1beta could be noted in the proximal stump epi-/perineurium and in the distal stump endoneurium. At that time point many macrophages were observed in the longitudinally sectioned epineurium of the proximal 2 area as well as in the cross-section slides from the distal stump. At day 35 TNF-alpha, IL-1beta and IL-10 mRNA appeared abundantly in the proximal epi-/perineurium together with macrophages. CONCLUSION: The present studies show that even during chronic denervation there is a cyclic expression pattern for the studied cytokines. Contrary to the previous findings on reinnervating nerves the studied cytokines show increased expression up to 35 days. The high expressions of pro-inflammatory and anti-inflammatory cytokines in the proximal epi-/perineurial area at day 35 may be involved in the formation of fibrosis due to irreversible nerve injury and thus may have relevance to the formation of traumatic neuroma.
Living with MS, I feel like a “Lab Rat” all the Drugs and stuff I have to take and do to keep going with this thing.
I’m not a Dr or have any Medical Degrees, but I see some of the Best Neuroloist in the Midwest, and I have heard alot of things but never this “Bug” thing.
But they all will basically admitt it from the Gulfwar, just like the VA wrote it up. Multiple Sclerosis Service Connected Gulf War Presumptive.