Monday, February 9, 2009

Aedes Mosquito bites as a treatment for Autoimmune?

Here is a weird piece of the evidence to add to the observation about the allergy/autoimmune "hygiene hypothesis" and the "farther north the more autoimmune disease in a population' observation.

The hygiene hypothesis takes note that the cleaner and more hygienic the housekeeper is in a particular household the more likely on average that the residents of the house hold will have autoimmune and allergic disease. It has been postulated that infections with certain bacteria, especially mycoplasma bacteria and infection with parasitic worms especially helmintes and nematodes reduce the incidence of autoimmune (and allergy). There is a fair amount of epidemiological evidence for this hypothesis. So if your Mom was a really good housekeeper than you were less likely to be exposed to the bacteria and intestinal parasites that many of us need to make our immune systems function normally. One way around it is to take toddlers to a working farm with large farm animals (horses, cows) and let the toddlers wander touch the ground and put their hands in their mouths. (All toddlers are compelled to put items in their mouths, the need for immune regulating bacteria and parasites seems a good explanation for this universal compulsion among our children.)

It has also been known from observations going back to the beginning of the twentieth century that the farther north a population lives the higher the incidence of autoimmune disease like RA, MS and Lupus in that population. This theory has been tied to lower intensity of UV light in the north and the more clothing worn in cold climates. UV light triggers the formation of Vitamin D. Vitamin D is rather low in our diets. Vitamin D has been shown to reduce symptoms of some forms of autoimmune disease. For instance, the FDA approved a Vitamin D3 cream for psoriasis on last Friday. Without a certain minimum of UV light hitting our skin we cannot make enough vitamin D to stay healthy. Low levels of Vitamin D were thought to be the reason for the higher incidence of autoimmune disease in northern populations (not to mention rickets).

However now we have another possibility for both the hygiene hypothesis and the observation about more autoimmune disease in the north, fewer Aedes mosquitoes. Yes that is correct. Fewer Aedes mosquitoes mean fewer mosquito bites that contain a long lasting IL-10 homologue. IL-10 when given in the correct concentrations and times can turn off autoimmune disease. It is thought that intestinal worm human parasites also produce an IL-10 homologue that helps them to evade our immune system by making it less likely to attack them. At the same time the IL-10 homologue also turns down the autoimmune and allergy response. Without the Aedes mosquito bites with their brew of immune modulating chemicals perhaps susceptible individuals develop autoimmune disease that they need not develop if the screens were off the windows.

Now we know that Aedes mosquitoes can produce a long lasting IL-10 homologue. See article below. The problem is that the IL-10 homologue makes a normal immune system less able to fight off West Nile infections. Yet if we could be bitten by a bunch of un-infected Aedes mosquitoes perhaps we could end our autoimmune and allergy problems. Who knows?

Is it time to take the screens off our windows, stop washing our hands after gardening, use human waste for fertilizer and always go barefoot? (The barefoot idea is so we can get infected with hook worms. The hook worm larva instantaneously burrow through the bottom of the human foot when stepped on. Hook worms are endemic and ubiquitous in the deep south in the United States also in parts of Mexico, Central America, tropical Africa and any other warm moist climate around the world.) I cannot help wondering if my son would be healthy today if we had allowed him to walk around barefoot outside in Western Kentucky (Graves County) as a child when we visited with my wife's relatives. On the other hand too many hook worms can cause severe anemia and some people's immune systems go nuts when exposed to worms--shock, urticaria, angioedema even death. So who knows.

We take Paul outside every day and he sits in the sun for as long as the bones in his deteriorating back allow. The natural vitamin D seems to help him. He has a tan now. Even without West Nile we could not allow him to be bitten by mosquitoes as even long ago before autoimmune when he was a healthy child mosquito and flea bites resulted in large welts followed by chicken pox like scabs and scars. We live only sixty miles from Mexico. If we only knew more maybe it would be a good idea to take him down there and let him walk barefoot in the Tijuana River bed which is a open sewer. Right now the risks outweigh the benefits.

But why am I not as ravaged by autoimmune as my son? It rips apart my gut on a regular basis. I have hives. My hands and neck swell. I have had several episodes of anaphylaxis which have left me close to death and once completely dead and gray but my joints work. My skin is unaffected. Why is my son so much worse than I am? Was it all the mosquito bites I have gotten over the years? Was it the years I spent in the sun as a distance runner from age of 12 until my mid thirties? Was it all the particular mosquito bites I got in the summer while camping at Tuolomne Meadows (Yosemite)? Was it running around barefoot as a kid? So many questions, so few answers.

Here is the article on the finding that Aedes mosquitoes produce an IL-10 homologue.

Source: University of Texas Medical Branch at Galveston
Thursday, November 15, 2007

There’s one more reason to try to avoid being bitten by mosquitoes, scientists have discovered: bites from mosquitoes that aren’t infected by the West Nile virus may make the disease worse in people who acquire it later from West Nile-infected mosquitoes.

Researchers from the University of Texas Medical Branch at Galveston (UTMB) announced their discovery in a paper published online by the journal PLoS ONE. In the paper, they describe experiments showing that lab mice on which mosquitoes have previously fed are far more likely to die from West Nile infection than are mice unexposed to such mosquito bites.

The effect is induced by mosquito saliva, according to UTMB professor Stephen Higgs, one of the paper’s senior authors.

“This virus is transmitted from mosquitoes in saliva, and we’d already demonstrated that mosquito saliva has an effect on the vertebrate immune system that makes West Nile infection worse,” Higgs said. “What this new work shows is that the saliva delivered by even earlier feedings can also alter the course of the infection. This is important, because in natural situations in many parts of the world – Southeast Texas, for example — animals and some people are being exposed to mosquito feeding almost continuously.”

In their experiments, researchers exposed sedated mice to feeding by between 15 and 20 Aedes aegypti mosquitoes for an hour once a week. Scientists then allowed a single West Nile virus-infected mosquito to feed once on each of these mice and also on each of a control group of mice that were previously unbitten by mosquitoes.

The results were striking: 68 percent of mice exposed to two weekly mosquito feedings died of West Nile virus, and those exposed to four weekly mosquito feedings suffered a 91 percent mortality rate. By contrast, the virus killed only 27 percent of the mice previously unexposed to saliva from mosquitoes that were free of West Nile infection. Analyses of responses of the mouse immune systems also showed a strong contrast between the previously exposed and unexposed mice.

“When we examined the immune reactions, one that stood out was an increase in the immune signaling molecule interleukin-10,” said Brad Schneider, the paper’s lead author and a UTMB alumnus who is now a postdoctoral fellow at the Institut Pasteur in Paris. “This host response to the saliva of the mosquito causes a shift in the immune response at the site where the virus first contacts the host, and the virus takes advantage of this shift.”

The UTMB researchers were surprised to find that mosquito bites seemed to have a detrimental effect with West Nile virus, because multiple earlier bites from other uninfected arthropods can actually protect against the parasites and bacteria carried by them. “Previous work has clearly indicated that pre-exposure to the bites of uninfected sand flies has a protective effect for mice against cutaneous leishmaniasis,” said Dr. Lynn Soong, the paper’s other senior author and an immunologist who works on the sand fly-transmitted protozoan parasite infection, dubbed “Baghdad boil” by American troops in the Middle East.

“Since this goes against the work we’ve seen with both bacteria and parasites, we definitely didn’t expect this result,” Schneider said. “But when we stood back and looked at it, it made sense. For a parasite or bacterium, the influx of immune cells brought in by this inflammatory response would be negative, but with the West Nile virus, you’re just giving it more susceptible cells to infect.”

Both Higgs and Schneider emphasized that the mouse experiments offered no definitive answers to the question of human responses to West Nile. “This is a mouse model, but that’s the best we’ve got at the moment,” Higgs said. “The thing is, it suggests that there may be yet another reason to avoid mosquitoes, to tidy up your yard and wear mosquito repellent

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