Anti-interleukin-15 prevents arthritis in Borrelia-vaccinated and -infected mice.
Amlong CA, Nardelli DT, Peterson SH, Warner TF, Callister SM, Schell RF.
University of Wisconsin, Wisconsin State Laboratory of Hygiene, Department of bacteriology, 465 Henry Mall, Madison, WI 53706, USA.
We showed previously that interleukin-17 (IL-17) plays a significant role in the induction of arthritis associated with Borrelia vaccination and challenge. Little information, however, is available about the chain of immunologic events that leads to the release of IL-17.
The production of IL-17 has been linked to stimulation of memory cells by IL-15. Therefore, we hypothesized that IL-15 is involved in the induction of arthritis associated with Borrelia vaccination and infection of mice.
Here we present evidence that treatment of Borrelia-vaccinated and -infected mice with anti-IL-15 antibody prevents swelling of the hind paws. More importantly, both anti-IL-15 antibody- and recombinant IL-15 receptor alpha-treated Borrelia-vaccinated and -infected mice were free of major histopathologic indications of arthritis, including hyperplasia, hypertrophy, and vilus formation of the synovium. Similarly, the synovial space and perisynovium were free of inflammatory cells.
By contrast, the synovium of nontreated Borrelia-vaccinated and -infected mice had overt hyperplasia, hypertrophy, and vilus formation. Moreover, the synovial space and perisynovium were infiltrated with neutrophils, macrophages, and lymphocytes.
Finally, we show that recombinant IL-15 stimulates the release of IL-17 from lymph node cells obtained near the arthritic site. These results suggest that IL-15 plays a major role in orchestrating IL-17 induction of arthritis associated with Borrelia-vaccinated and -infected mice.
PMID: 16467340 [PubMed - indexed for MEDLINE]
Posted by lou (Member # 81) on :
up for people with bad outcome from lyme vaccine
Posted by sofy (Member # 5721) on :
Thanks so much. Do you know what this says as far as a possible treatment strategy?
Posted by lou (Member # 81) on :
I don't know that it has gotten as far as actually treating human patients. So far they have only looked at mice. But it certainly suggests that there might be a human application. I presume that these researchers have it in mind. At least one of them was involved in research that showed there was such a problem with the vaccine initially.
As you probably know, research is just looking at possibilities, some will work out, some will not.
If I had vaccine damage, though, I would sure be paying attention to this kind of research.
Posted by lou (Member # 81) on :
Here's another one on the same subject, a year earlier. So, they are definitely looking at the problem. Do you know how to search pubmed? You could look up the previous papers of Callister and Schell and see what they say.
Or just wait a while and see if any human treatment applications come from their research.
I guess what I'm saying is that maybe vaccine caused arthritis might be treatable, don't give up hope that they will find something to help you.
Clin Diagn Lab Immunol. 2005 Jun;12(6):786-92.
CD4(+) CD25(+) T cells prevent arthritis associated with Borrelia vaccination and infection.
University of Wisconsin, Wisconsin State Laboratory of Hygiene, 465 Henry Mall, Madison, WI 53706, USA.
CD4(+) CD25(+) T cells are a population of regulatory T cells associated with control of arthritis in anti-interleukin-17 antibody-treated Borrelia-vaccinated and challenged gamma interferon-deficient mice. Here, we present direct evidence that adoptive transfer of enriched CD4(+) CD25(+) T cells from these mice can prevent the development of arthritis in Borrelia-vaccinated and challenged mice. These findings establish a major role for CD4(+) CD25(+) T cells in the prevention of arthritis in Borrelia-vaccinated and challenged animals.
PMID: 15939755 [PubMed - indexed for MEDLINE]
[ 15. April 2006, 01:26 PM: Message edited by: lou ]
Posted by lou (Member # 81) on :
Here was their research showing the vaccine could cause damage:
Infect Immun. 2000 Feb;68(2):658-63.
Comment in:
* Infect Immun. 2000 Dec;68(12):7212-3.
Occurrence of severe destructive lyme arthritis in hamsters vaccinated with outer surface protein A and challenged with Borrelia burgdorferi.
Croke CL, Munson EL, Lovrich SD, Christopherson JA, Remington MC, England DM, Callister SM, Schell RF.
Wisconsin State Laboratory of Hygiene, University of Wisconsin, Madison, Wisconsin 53706, USA.
Arthritis is a frequent and major complication of infection with Borrelia burgdorferi sensu stricto. The antigens responsible for the induction of arthritis are unknown.
Here we provide direct evidence that a major surface protein, outer surface protein A (OspA), can induce arthritis. Hamsters were vaccinated with 30, 60, or 120 microg of recombinant OspA (rOspA) in aluminum hydroxide and challenged with B. burgdorferi sensu stricto isolate 297 or C-1-11.
Swelling of the hind paws was detected in 100, 100, and 50% of hamsters vaccinated with 30, 60, or 120 microg of rOspA, respectively. In addition, arthritis developed in 57% of hamsters vaccinated with a canine rOspA vaccine after infection with B. burgdorferi sensu stricto.
When the canine rOspA vaccine was combined with aluminum hydroxide, all vaccinated hamsters developed arthritis after challenge with B. burgdorferi sensu stricto. Histopathologic examination confirmed the development of severe destructive arthritis in rOspA-vaccinated hamsters challenged with B. burgdorferi sensu stricto.
These findings suggest that rOspA vaccines should be modified to eliminate epitopes of OspA responsible for the induction of arthritis. Our results are important because an rOspA vaccine in aluminum hydroxide was approved by the Food and Drug Administration for use in humans.
PMID: 10639430 [PubMed - indexed for MEDLINE]
Posted by Marnie (Member # 773) on :
So...BLOCKING IL 15 prevented the disease from getting a foothold in mice.
Humm..I was gonna go swim in my pool, but this drove me nuts...I needed to try to figure it out.
Okay...here goes:
First...
IL-15 stimulates NK (natural killer) cell proliferation and proliferation of T-lymphocytes.
If we BLOCK IL 15, then no/fewer NK cells.
Now the NK cells are the "first on the scene"...way before - days - the T (as in thymus) cells.
They work by sorta squirting a free radical at the offender.
Another way to block them, to decrease their numbers...
exercise - strenuous.
Okay...what do we make when we exercise...a lot?
Lactic acid.
There's a clue.
Now...Bb breaks down fats to supply glycogen -> ethanol which I think finally reduces to lactic acid...hence the really tired feeling, muscle aches and pains (along with low choline contributing to the spasms).
Bb shys away from ethanol.
Is Bb using Zn to protect itself from ethanol?
"Zinc is necessary for the proper metabolism of alcohol, to get rid of the lactic acid that builds up in working muscles and to transfer it to the lungs."
Is this a matter of lactic acid fermentation competing with alcohol fermentation?
If we can chelate Zn really fast...via lactic acid...
And then there's the calcium - lactic acid component...No wonder it goes up...the body is trying to halt this. (PMID: 2731366)...drop Ca levels and thus conserve Mg loss due to Bb's PKC inhibitor (competes with Mg-ATP).
Now what if too late? Or is it?
� Glucagon does not cause a rise in glucose levels, but it does raise lactic acid levels.
� Oral galactose and fructose fail to increase glucose levels but plasma lactic acid levels increase.
The lactic acid system is capable of releasing energy to resynthesise ATP - ATP Inactivates PFK 1 - without the involvement of oxygen and is called anaerobic glycolysis. Glycolysis (breakdown of carbohydrates) results in the formation of pyruvic acid and hydrogens ions (H+).
A build up of H+ will make the muscle cells acidic and interfere with their operation so carrier molecules, called nicotinamide adenine dinucleotide (NAD+), remove the H+. The NAD+ is reduced to NADH which deposit the H+ at the electron transport gate (ETC) in the mitrochondria to be combined with oxygen to form water (H2O).
If there is insufficient oxygen then NADH cannot release the H+ and they build up in the cell. To prevent the rise in acidity pyruvic acid accepts H+ forming lactic acid which then dissociates into lactate and H+. Some of the lactate diffuses into the blood stream and takes some H+ with it as a way of reducing the H+ concentration in the muscle cell.
The normal pH of the muscle cell is 7.1 but if the build up of H+ continues and pH is reduced to around 6.5 then muscle contraction may be impaired and the low pH will stimulate the free nerve endings in the muscle resulting in the perception of pain (the burn).
This point is often measured as the lactic threshold or anaerobic threshold or onset of blood lactate accumulation (OBLA).
Glucagon inhibits PFK 2 in the liver.
Catalase. Anti-oxidant enzyme.
"Evidence that catalase is a major pathway of ethanol oxidation in vivo."
"The possibility of catalase playing a metabolic and potentially protective role in rat myocardium chronically exposed to ethanol is discussed. "
"inhibition of brain catalase increases ethanol-induced plasma corticosterone levels."
"The action of the enzyme catalase on aqueous hydrogen peroxide to generate oxygen gas is a well-established demonstration."
"The enzyme catalase is part of most organisms' defense against the superoxide radical anion, O2-, a harmful by-product of the metabolic oxidation of fats and carbohydrates (4). The enzyme superoxide dismutase is the first line of defense against O2-. It converts superoxide ion to hydrogen peroxide, which is still quite toxic to cells.
Catalase is responsible for converting the hydrogen peroxide to water and oxygen"
2O(2)- plus 2H + ...superoxide dimutase...H(2)O(2) + O(2)
2H(2)O(2)...catalase...2H(2)O(2) + O(2)
The parenthesis above...drop the # down.
O(2) is the harmful byproduct. See how 2 harmful O(2)-s combine with 2Hs to yield H(2))O(2) - hydrogen peroxide and O(2) via S.O.D. (an antioxidant enzyme)
(Research SOD and Bb...Bb does NOT contain catalase.)
Then 2H(2)O(2)...via catalase yield 2 H(2)O - water -and O(2).
So...2 harmful O(2)s are reduced via these antioxidant enzymes. In the process...hydrogen peroxide is made...then water and oxygen.
"The results showed that during 72 h of magnesium-deficient treatment, the H2O2 release from the cells gradually increased
and consumption of exogenous H2O2 was enhanced during the first 48 h of treatment.
GSH content gradually decreased but GSSG was not affected.
The activity of glutathione reductase was first stimulated and then inhibited.
Catalase activity was gradually reduced.
14C]Amino acid mixture release from the cells continuously increased.
We suggest that magnesium deficiency affected the intracellular antioxidant system in cultured endothelial cells.
PMID: 10192096
"N-acetyl cysteine attenuates ethanol induced hypertension in rats."
"N-acetylcysteine attenuates alcohol-induced oxidative stess in rats."
Simplified...NAC looks to HELP.
"Acetaldehyde, a metabolite of ethanol, activates the hypothalamic-pituitary-adrenal axis in the rat."
Acetaldehyde-induced increases in malonaldehyde were reduced by pre-incubation with antioxidants such as Vitamin E (200 mg%) or glutathione (100 mg%)."
Translation: looks like Vit E (which we know drops) and glutathione can HELP.
Looks like we gotta protect the liver and brain from the excess ethanol.
Desferrioxamine (5-10 microM) completely abolished alkane production induced by both ethanol and acetaldehyde, indicating the importance of catalytic iron. Thus free radicals generated during the metabolism of acetaldehyde by aldehyde oxidase may be a fundamental mechanism in the initiation of alcohol-induced liver injury.
PMID: 2363695
Did the lactic acid "dissolve" the zinc-protein finger of Bb? Not allowing it to lock on?
(Acids dissolve minerals...usually it takes a lot of acids to do this...deplete the minerals.)
Acid errosion of various dental cements:
In lactic acid, zinc phosphate and zinc polycarboxylate cements showed a gradual reduction in mass throughout the six weeks... PMID: 15348686
Time for a swim. Gotta get my exercise and vitamin D.