posted 21 March 2005 12:13               

Yet none who claim to have achieved this 'cure' have stopped taking Benicar.

We know that many people have taken Benicar at MP doses combined with high doses of antibiotics. The 'potentiated' mega-herx that should have ensued did not.

The official explanation - that tiny, homeopathic doses of antibiotics devastate bacteria but inhibitory concentrations do not - is simply not credible. Elizabeth concedes this.

So why does she repeat the claim?

Not because of something she has read in Marshall's papers. I have read them, read each several times, read many of their referenced materials (which often contradict the claims they are invoked to support).

It was precisely by reading those papers closely that I discovered I had been sold a bill of goods.

So why? Why is the claim repeated?

When patients report an exacerbation of symptoms in response to a given behavior (it hurts when I do this) the common sense answer is 'don't do that'.

Elizabeth has said repeatedly now that this answer does not apply to symptom exacerbation experienced on the MP, because antibiotics are being potentiated and infection is being cleared.

Elizabeth, this is not an academic question. You propose to offer guidance to patients who either are, or are not, helping themselves by combining massive doses of Benicar, D-deprivation and sub-inhibitory doses of antibiotics.

You have participated in an enterprise that tirelessly assures patients who feel worse on this regimen, 'not to worry, you may feel worse but you are certainly GETTING better.'

Here, in this forum, where all anyone asks is that you be candid, you have been asked a straightforward question: on what BASIS do you say that these patients are getting better?

All that is asked, Elizabeth, is that you clearly indicate whether you have a rational basis for that claim, or are articulating a belief, grounded in faith, not fact.

posted 21 March 2005 12:14               

quote:

---

Originally posted by TX Lyme Mom:
This is what the...approach is uniquely qualified to deal with -- namely, granuloma formations and also intracellular pathogens, which have paralyzed the host's immune system's ability to function properly.

---

Uniquely Qualified. Uniquely Qualified?

On what basis should an experimental treatment be considered "qualified" to deal with intracellular pathogens? I would think to "qualify" there would first have to be a diagnosis of identifiable pathogens and then undisputable evidence that the pathogens are eradicated with treatment, at least in a portion of the patients. Barring that, then some good hard statistics of full remission?

I don't mind people having their opinions, or their theories. I don't mind optimism, but if opinion is going to be shrouded in scientific sounding mumbo jumbo and unsubstantiated claims, then I'm going to demand some accuracy, because this kind of stuff is misleading and is exactly the reason so many people buy into something without understanding it.

This is like political double speak. If you really care about people as you claim, you'll stop it, you'll stop glossing over the evidence you have of people you say were "harmed" and start telling the truth. "Helping people" should be completely egoless, who cares what others think of you? Otherwise it's a corrupted activity. So far, I feel like I'm right back where we started months ago, where concern for struggling patients comes last, especially if they get in the way of our personal agendas. (Oh, except the language has been cleaned up, prettified for prime time viewing.)

posted 21 March 2005 12:33               

What's really sad, is that all the conjecture and hyperbole and spin is probably doing way more damage than good. It's completely clouding, and potentially damaging, the kind of work being done by great researchers like Gary Smith and colleagues.

I'm sure Sankyo and other ARB manufacturers are none too pleased by these whacko developments surrounding their drugs. It's totally impossible to determine what's true and what isn't based on this kind of dialogue.

We need to focus on science, on evidence, on the potential benefits and the potential harm, and stop getting side tracked by the particular biases of certain individuals. We are sorely in need of objectivity, and we need the support of companies like Sankyo. That means moving forward with objective investigation, not dogma and blind belief. The sooner we can discuss this objectively, the sooner progress will be made. Which of course is what we were trying to do at Infection and Inflammation, despite numerous claims that open discussion was "harming patients". Of course, that's before we got "mysteriously" shut down.

posted 21 March 2005 13:06               

I did read Marshall's work early on and I saw that he cited a paper where half the sarc patients improved on Vitamin D and half got worse. I asked him about this and I never got a good answer. I posted on his list a roundup showing the importance of Vitamin D.

I don't doubt some people have excess Vitamin D metabolites. But I don't think its the majority and I don't think staying out of the sun longterm is a good idea. Killing the infection is a better idea.

posted 21 March 2005 13:28               

quote:

---

Originally posted by TX Lyme Mom:
I'll try to address some of the other in-depth scientific concerns to the best of my ability, as time permits. I have several other pressing matters to attend to today, so my time at the computer is still very limited right now.

Therefore those issues, which require a lot of time to compose complicated responses to, will simply have to wait for another more convenient time for me to address them, later.

---

I had every good intention of coming back to this topic later, when I would have adequate time to discuss these ideas in greater depth, but I have concluded that this is turning into an unnecessarily confrontational argument, frought with negativity.

Anything further which I might have intended trying to say here in this forum would only prove to be a complete waste of time for everyone.

Each person is free to draw whatever conclusions of his or her own about the potential value of the MP -- but NO one should claim to draw any conclusions whatsoever about what my own views might be on any of the unanswered questions which I did not have sufficient opportunity to address previously, because that would me a most unfair thing to try to do.

posted 21 March 2005 14:45               

quote:

---

Originally posted by TX Lyme Mom:
[B] I had every good intention of coming back to this topic later, when I would have adequate time to discuss these ideas in greater depth, but I have concluded that this is turning into an unnecessarily confrontational argument, frought with negativity.

Anything further which I might have intended trying to say here in this forum would only prove to be a complete waste of time for everyone.

Each person is free to draw whatever conclusions of his or her own about the potential value of the MP -- but NO one should claim to draw any conclusions whatsoever about what my own views might be on any of the unanswered questions which I did not have sufficient opportunity to address previously, because that would me a most unfair thing to try to do.[B]

---

Maybe you should have thought of that, back when we tried to follow the very same principles at I & I, but instead were continously vilified and attacked, and eventually shut down.

Forgive me if I don't feel like sitting here now and hearing how pretty everything is. If you really don't want to waste people's time, then try to get real.

penny

posted 21 March 2005 14:47               

penny

posted 21 March 2005 15:16               

This started out as a good thread. So much so that I almost got up the courage to share my experience with 10 months on the MP. Now I remember why I choose lurk mode on these lists.

Can't those of you who are so angry (rightfully so), see how in your passioned attempts to preserve our right of free speech and help/protect others you are creating the same negative atmosphere by a different route?

If you can't find your way to forgiveness, at least get out of the way and let people express their experiences and opinions. And I don't mean opinions about other people's intentions, motives or agendas, just opinions about the protocol, and the research.

"Know won nose" (if you don't read phonetically, say it aloud)

posted 21 March 2005 16:08               

"you will understand that my peer-reviewed publications lend my opinion a certain credibility, and international reputation"

Attempt at humor

* So he has gotten a bunch of PhD's in Electrical Engineering to review his work?

* Or, did he post it on a board of people with the same illness (and thus obtained review from his peers)? Gee whiz, all of us have peer-reviewed literature now!

* I recall that someone pointed out that he owns the "journal" where his stuff is published. Any critical comment on it would not be published.

So my opinion about the research is that it is likely far less worth than reading CFS-L; and there is such an appearance of a lack of any intregity in Trevor Marshall that any research claim should be validated independently before being acted upon.

quote:

---

Originally posted by Digby:
just opinions about the protocol, and the research.

"Know won nose" (if you don't read phonetically, say it aloud)

---

posted 21 March 2005 18:19               

Now, I will proceed to my main topic of the science of vitamin D, which is a complex and difficult one and was brought up at some length by Paul.
I know this post is somewhat long and technical and may be difficult for readers who are not very familiar with the subject. One might look at the vitamin D article I mention (where many of the references can be found) and also an overview article of the MP that I wrote for Issue 7 of CISRA’s Synergy Health Newsletter at members.aol.com/SynergyHN. I tried to make the overview article somewhat simpler.

By the way, although I am doing well on the MP myself, I am still independent and write on a variety of subjects, and do my best to study the science, sort things out and write them up to the best of my ability.

Like Paul, I have been researching the topic and trying to learn to what extent Trevor Marshall’s data and views can be reconciled with other studies supporting more widespread vitamin D supplementation.

First, I will address the issue of why some people at the MP sites with normal levels of 25 D and 1,25 D are being told the protocol is still appropriate for them. For one thing, as time has passed, they have found that in people with a clinical picture compatible with the MP and with these normal levels, they still tend to respond in the same way to the MP drugs. So now, they view the D tests as useful as indicating to a rough degree the degree of inflammation in areas of the body with plenty of blood flow (like heart and lungs), but perhaps more importantly, as a tool to rule out a TH2 viral process like AIDS or chronic hepatitis, where the 1,25 D was truly very low.

As Marshall explains, the paracrine or local levels of 1,25 D in areas with less blood flow, like joints, may be much higher. In addition, the body has a certain level of regulatory ability, particularly in the kidneys. If peripheral tissues are producing extra 1,25 D, most people’s kidneys have the ability to slow production of 1,25 D in order to compensate and thus have the end result of a normal serum level. However, beyond a certain point and perhaps more so in different people (perhaps with more kidney inflammation?), this compensatory regulatory ability is exceeded by the unregulated production of 1,25 D in inflamed tissues.

My personal experience has been that I had been taking about 600-1000 IU vitamin D in supplements for most of my illness. Last August, when I had my D levels tested, my 25 D was fairly low at 11 ng/ml, but my 1,25 D was elevated at 65 pg/ml, well above the Merck maximum of 42, though near many lab’s normal upper end. Thus, inflammation was causing a rapid conversion of 25 D to 1,25 D, just as in sarcoidosis.

My serum calcium levels were not the slightest bit elevated, so there appeared to me to be no reason to suspect that my 1,25 D was so high based on traditional criteria (this is usually the case with regard to serum calcium and 1,25 D values, according to Dr. Marshall’s data). The calcium levels are of importance, since most of the reviews supporting higher vitamin D supplementation say that one can avoid excess 1,25 D levels by monitoring serum calcium, which they say will identify excess D levels. The new data being posted at the MP sites and published by Marshall show this is not an adequate way of monitoring for high 1,25 D.

I was surprised how much better I felt when I began avoiding D and sun and then began the Benicar. Of course, for some people, who’s immune systems are in a different stage, they may feel worse on lower vitamin D. According to the MP theory, this is because the Herx symptoms may increase once the D is lower and the immune function begins killing the bacteria. Despite short term improvements, the potential for a later relapse may be there as the bacteria are able to continue to increase unhindered. And so it seems, if one is to evaluate whether the MP theory is correct, that short term improvements in a variety of studies may need to be reexamined, as the vitamin D may have been acting in a manner somewhat analogous to high doses of prednisone at least in certain illnesses (though it apparently differs from prednisone in that it mainly suppresses CWD bacterial killing, not all immune function).

According to Marshall, the above phenomenon of Herx suppressions can explain the improvement in many of the studies that claim vitamin D to be beneficial. In many cases, this seems to me to be feasible, though more data is needed. The studies are too short term to know if there is an ultimate benefit to this increased D level or if there would be an ultimate relapse. Even studies showing seasonal variation in MS lesions could be showing a process similar to what would happen if the patient was given immunosuppressive drugs only in the summer (instead of the greater sun exposure).

Regarding MS, I have several points to make (see article from Issue 7 at members.aol.com/SynergyHN for references). First, I think it may be true that very low levels of vitamin D that truly reflect a deficiency of active 1,25 D as well as the inactive precursor 25 D, might lead to a greater incidence of people getting MS to begin with. I see this as possibly being due to the fact that as with other hormones, we all need a level of 1,25 D in a certain range surrounding the mean for normal functioning. In far northern latitudes, where people, particularly older people are indoors or almost entirely covered up for a large part of the year, this may not happen, unless they consume enough vitamin D containing foods. But this doesn’t necessarily mean that once one has MS, and the macrophages may be producing a lot of 1,25 D in response to CWD bacteria, that one would benefit by having so large an amount of vitamin D that it suppresses immune function.

Second, to my knowledge, only one epidemiological study seems to show that there is better survival for MS patients who have outdoor jobs and thus presumably more vitamin D. I will just say that these kind of epidemiological studies have a lot of potential for bias. For instance, people choose their jobs for all sorts of reasons that could correlate with characteristics of their disease and influence the results, and I think it unwise to base too much on this study alone.

However, even if it turned out that this study’s conclusions were validated, it may just mean that immune suppression with high D limited inflammatory damage to some degree and extended their life a little longer (as opposed to sarcoidosis, where it would seem to be more likely to hasten their death). But that doesn’t mean that low D plus the MP’s treatment or perhaps other antibacterial treatment of a proposed bacterial cause wouldn’t have far better results than giving just vitamin D. Perhaps the antibiotic based treatments might even cure the disease.

As for the animal studies showing a benefit of vitamin D in autoimmune illnesses, there are also many problems. The mouse model for the autoimmune diseases involves causing a condition that looks similar to MS or other AI diseases by injecting certain antigens into the animal. It may be that they are able suppress the immune reaction to the antigens with too much vitamin D, and if this is the case, it is not surprising that the disease would improve. But, if this is not a true model of the disease, but it is actually caused by bacteria that would eventually proliferate more with immune suppression, the mice experiments are probably of little value. There are other problems too, like the experiments are short and mice are adapted to much dirtier environments, but I personally find the first reason most convincing.

I have also begun looking at the data for cancer, especially looking at the work of William Grant, Ph.D., (www.sunarc.org) who does a lot of epidemiological cancer research. He sent me a very recent paper he wrote where he discusses data that shows that prostate cancer rates had a J shaped relationship with light intensity (Int. J. Cancer. 111:470-471, 2004). His brief article also cited a paper (Tuohiman et al., Int. J. Cancer 108:104-8, 2004) that showed the lowest prostate cancer rates were in the range of 40-60 nmol/l (about 16-24 ng/ml) and this was supported by the correlation being J shaped when looking at the relationship between living at various latitudes and prostate cancer.

This J shaped curve suggests that people with too high a level of vitamin D are more prone to get prostate cancer than those in the moderate range for D. For the study that actually measured 25 D, those with too low a level of 25 D (the inactive precursor) could reflect two different situations, and perhaps both may occur. The very low 25 D may be associated with a true deficiency and in that case the active hormone, 1,25 D would also be very low and supplementation might be appropriate. However, the 25 D could also be low due to a TH1 inflammatory process depleting the 25 D precursor through conversion by macrophages into 1,25 D. In that case, the 1,25 D would then be high and supplementation would be inappropriate. Clearly, these two different possibilities to explain low 25 D can not be distinguished until studies start also measuring 1,25 D.

I do think that the studies that showed evidence for higher colon cancer mortality rates in parts of the world with very low light levels might suggest that very low levels of sun exposure might increase the colon cancer mortality rate, especially since calcium deficiency has also been linked independently with colon cancer (Grant et al, Nutrition and Cancer 48(2): 115-123.) It may be, however, that if everyone got adequate calcium, that the D levels would no longer be a factor. It is also interesting that the above relationship for colon cancer did not hold up for women, when the data were analyzed separately in several studies. It seems to me that the higher rate of autoimmune and related diseases in women, (presumably the undiagnosed cases, as obvious cases would probably have been excluded from the study) might have caused the correlation to disappear. In women, the 1,25 D levels might be more frequently elevated due to TH1 disease, so even very low light exposure would not cause them to be deficient.

For breast cancer, the relationship with D was weaker, and other dietary factors seemed to be much more important (Grant, Cancer 94:272-81, 2002). I have yet to look further into this data, but I thought it interesting that I have seen maps of the U.S. showing breast cancer in the areas of highest industrial activity (CIIN conference, 2004, ciin.org). These areas were in the Northeast, especially. This relationship might confound the vitamin D effect for the U.S., as a large part of the breast cancer correlation was related to finding higher cancer rates in the Northeast, as compared to the Southwest. But I need to look into this more.

Another area I plan to look into is the relationship some have observed between sun exposure, vitamin D and depression. I know my own mood fluctuations have improved since I lowered D, while others have responded differently. The link between inflammation and depression and other mental disorders has received a lot of interest of late. Many of us experience this link when we undergo Herx reactions and feel rather depressed and/or anxious, even having bad dreams on the nights of our biggest Herxes due to the antibiotics. I intend to look further into this in future, but it seems possible that at least some cases of depression being helped by sun or vitamin D could be due to high levels of D suppressing the inflammation from Herxes (occurring when the immune system kills CWD bacteria).

I plan to write a more detailed article on these issues in the coming months, but I thought I’d share these preliminary observations. I hope they may be of some help in giving a different perspective on this complex subject.

posted 21 March 2005 19:33               

FIRST: Would you please give some MEDLINE citations that validates this speculation that 1,25D is a valid indicator for TH1 / TH2 determination?

--------------------------
SECOND, I see from the literature that HIV patients will often have 1,25 levels of 45 pg/mL (actually 25% are still higher than THAT).
[U]Subnormal serum concentration of 1,25-vitamin D in human immunodeficiency virus infection: correlation with degree of immune deficiency and survival.[/U]Haug C, Muller F, Aukrust P, Froland SS. J Infect Dis. 1994 Apr;169(4):889-93.

What confuses the matter even more is that the lowest levels of 1,25D are seen with HIV patients that have a Mycobacterium infection (which ain't a viral infection).

[U]Disseminated Mycobacterium avium complex infection in AIDS: immunopathogenic significance of an activated tumor necrosis factor system and depressed serum levels of 1,25 dihydroxyvitamin D.[/U] Haug CJ, Aukrust P, Lien E, Muller F, Espevik T, Froland SS. J Infect Dis. 1996 Jan;173(1):259-62.

Looking at the posted numbers on Marshall Protocol.com for 1,25D, I see SIXTY FIVE people (of 125 checked) with lower levels than seen with HIV, yet Trevor Marshall deem them to be candidates!!! 1,25 D levels are a poor differiator -- since you have a stats background:
What value is the critical value?
What is the alpha error risk with this vlaue?
What is the beta error risk with this vlaue?

Inquiring (trained) minds want to know

Where is he and you getting your numbers and literature from?????? You wrote up a storm, Trevor talks up a strom -- but upon inspection there seems to be nothing but speculation.
---------------------

quote:

---

Originally posted by joycejcwat101:
but perhaps more importantly, as a tool to rule out a TH2 viral process like AIDS or chronic hepatitis, where the 1,25 D was truly very low.

---

posted 21 March 2005 20:16               

I also agree that a study of the long-term response of MS to outdoor avocation does not really yield. You dont mention whether the authors tried to do a matched control group - but even if they did I dont see how it could ever have been "matched enough," given that many salient indices of mild MS are quite subjective [edit: and may be the very same indicies/phenomena that might affect a sickies decision on whether to take an outdoor job, since most of them are physical].

You dont mention whether you started D-avoidance and benicar simultaneously - if so one wonders if the effect on your symptoms might not have been solely from benicar.

In any case, it may be impossible to demonstrate that rapid effects of D-modulation on symptoms are not simply due to reversal of hypervitaminosis D. Hence I dont see any clear evidence that 1,25d can actually act as a pro-inflammatory (contrary to its usual effect) in our diseases of interest - ie human inflammatory diseases that are probably due more (as we all tend to believe) to alloimmunity than to autoimunity.

Regardless of by what mechanism D-avoidance may improve sx in the short run for *some* people (the contrary for others)... the question remains as to whether it is ultimately of larger benefit in vanquishing infections. I realize you havent addressed that yet here. But - regarding this question there are no nitty-gritty immunological-molecular proposals to explore; there is only what I would call hopeful speculation. Hence there are really only patient reports to go on.

Eric Hodologica, contemplator of bacteria

posted 21 March 2005 20:37               

Merck states:
". In healthy persons .. 20 to 45 pg/mL (48 to 108 pmol/L) for 1,25(OH)2D3." http://www.merck.com/mrkshared/mmanual/section1/chapter3/3d.jsp
Why the ALARMIST phrasing of Merck maximum of 42?

Vitamin D status: effects on parathyroid hormone and 1,25-dihydroxyvitamin D in postmenopausal women" Am J Clin Nutr 2000;71:1577–81. shows 135pmol/L (or 54pg/ml ) occuring in that population.

And I see many readings over 200 pmol/L (80pg/ml) in this newer article...

Age-Related Changes in the 25-Hydroxyvitamin D Versus Parathyroid Hormone Relationship Suggest a Different Reason Why Older Adults Require More Vitamin D J Clin Endocrinol Metab, January 2003, 88(1):185–191 REINHOLD VIETH, YASMIN LADAK, AND PAUL G. WALFISH

For example, deeming the normal level to START at 100 (which is above the Merck maximun)

Functional indices of vitamin D status and ramifications of vitamin D deficiency Am J Clin Nutr 2004;80(suppl):1706S–9S. Robert P Heaney,

Would it not be better to get the 25D up to to 100 before you do 1,25D testing?

quote:

---

Originally posted by joycejcwat101:
Last August, when I had my D levels tested, my 25 D was fairly low at 11 ng/ml, but my 1,25 D was elevated at 65 pg/ml, well above the Merck maximum of 42, though near many lab’s normal upper end.[B]

---

posted 21 March 2005 20:57               

"Know won nose" (if you don't read phonetically, say it aloud)

posted by digby

********************************************

There are so many valuable points for contemplation here, and of interest both extrapalated from various research points and patient experience.

I hope we can stick to focusing on those things, because surely there could be great value in open, respectful discussion.
Even in as much as understanding the bacteria/immune relationship..
as well as what to do about it.

Despite all the questions this approach has created, it is certainly a new and refreshing angle from which to learn from and perhaps apply.

That said..I have wondered whether there have been..or would be patients who could run basic CBC's, WBC with Dif.. and reactive Lymphocytes, immune complexes, C-reactive protein and SED rate, platelets (making new blood) as well as comprehensive metabolic panel (watch energy, liver, kidney health)..as a means of tracking what is going on.

If patients and Docs would be willing to run these orders...say...weekly...
perhaps some insight into whether herxing (in those cases/situations where there is uncertainty)...perhaps some insight into whether infection killing, die off, immune response is taking place in and around the time that herx reactions are experienced?

I wondered this some time ago when the discussions were new, and understood that..at the time..or for Sarc patients..
the bulk of testing was leaning upon the D tests..but really wonder if TBD's patients would have more to follow along these lines.

I have also branched off in some immunotherapy study for some time (where I landed after choosing/needing to pull myself out of Marshall discussions, actually)..
and this is what one might track in straight immunotherapy and infection.

This could apply to an immune-modulating therapy (where by the immune system is to be ultimately causing the herx activity)..in a much diferent way than if we follow these results in high dose abx therapy..
where the abx's do most of the work, and often times other immune system activity is dampened (ie: the immune system takes a break as the abx does the work)..

Just a random thought..

There could be reason's why this would not apply using the MP that I am not aware of.

Mo

posted 21 March 2005 21:06            

Before you can use test result data, and draw conclusions from that data, the data has to be clean.

The literature shows that 1,25D3 fluctuates throughout the ovulation cycle of fertile women (Reference 1)
and testosterone (Reference 2).

Therefore, at the very least, before you can use the results from 1,25 D3 testing for any analysis from which conclusions are drawn, the tests have to be standardized for these hormonal differences.

The labs that do these tests do not standardize for hormonal fluctuations.
so
comaring these levels amongst women of different age and hormonal status groups and men is not comparing apples to apples...

REFERENCE (#1)
PMID: 6897337 [PubMed - indexed for MEDLINE]

Am J Obstet Gynecol. 1982 Dec 15;144(8):880-4.
Fluctuation of serum concentration of 1,25-dihydroxyvitamin D3 during
the menstrual cycle.

Gray TK, McAdoo T, Hatley L, Lester GE, Thierry M.
________________________________________

REFERENCE 2

PMID: 9115169 [PubMed - indexed for MEDLINE]
: Calcif Tissue Int. 1997 May;60(5):485-7.

The metabolism of vitamin D3 in response to testosterone.

Otremski I, Lev-Ran M, Salama R, Edelstein S.

Biochemistry Department, The Weizmann Institute of Science, Rehovot,
Israel.

posted 21 March 2005 21:17               

I was talking about using basic methods to track immune system activity and infection.
..not specifically about the D testing, of which I admittedly know little about.

If I were to try the protocol, I'd want to follow these tests I listed just to see what I could see..

of course, not knowing till I saw it..or not..

posted 21 March 2005 21:40            

There are people who have Ploymorphous Light Eruptions (PLE)...
Very Very common with Lupus - and Sarc.. and one of the
hypersensitivites from chronic inflammatory conditions. And I guess 20% of the healthy
population suffers from this condition at one time or another.

The Journal of Immunology, Vol 149, Issue 12 3865-3871, Copyright ©
1992 by American Association of Immunologists

----------------------------------------------------------------------
----------

ARTICLES

Systemic suppression of delayed-type hypersensitivity by supernatants
from UV-irradiated keratinocytes. An essential role for keratinocyte-
derived IL-10

JM Rivas and SE Ullrich
Department of Immunology, University of Texas, M. D. Anderson Cancer
Center, Houston 77030.

Exposing murine keratinocyte cultures to UV radiation causes the
release of a suppressive cytokine that mimics the immunosuppressive
effects of total-body UV exposure.

Injecting supernatants from UV- irradiated keratinocyte cultures
into mice inhibits their ability to generate a delayed-type
hypersensitivity reaction against allogeneic histocompatibility Ag,
and spleen cells from mice injected with supernatant do not respond
to alloantigen in the in vitro MLR.
A unique feature of the immunosuppression induced by either total-
body UV- exposure or injecting the suppressive cytokine from UV-
irradiated keratinocytes is the selectivity of suppression.

Although cellular immune reactions such as delayed-type
hypersensitivity are suppressed antibody production is unaffected.
Because the selective nature to the UV-induced immunosuppression is
similar to the biologic activity of IL- 10, we examined the
hypothesis that UV exposure of keratinocytes causes the release of IL-
10.

Keratinocyte monolayers were exposed to UV radiation and at specific
times after exposure mRNA was isolated or the culture supernatant
from the cells was collected. IL-10 mRNA expression was enhanced in
UV-irradiated keratinocytes. The secretion of IL-10 by the irradiated
keratinocytes was determined by Western blot analysis. A band
reactive with anti-IL-10 mAb was found in supernatants from the UV-
irradiated but not the mock-irradiated cells. IL-10 biologic activity
was determined by the ability of the supernatants from the UV-
irradiated keratinocytes to suppress IFN-gamma production by Ag-
activated Th 1 cell clones. Anti-IL-10 mAb neutralized the ability of
supernatants from UV-irradiated keratinocytes to suppress the
induction of delayed-type hypersensitivity in vivo. Furthermore,
injecting UV- irradiated mice with antibodies against IL-10 partially
inhibited in vivo immunosuppression.

These data indicate that activated keratinocytes are capable of
secreting IL-10 and suggest that the release of IL-10 by UV-
irradiated keratinocytes plays an essential role in the induction of
systemic immunosuppression after total-body UV exposure.

___________________________________________________________________

Differential Expression of Cytokines in UV-B–Exposed Skin of Patients
With Polymorphous Light Eruption
Correlation With Langerhans Cell Migration and Immunosuppression

Wendy Kölgen, MSc; Marjan van Meurs, BSc; Marjan Jongsma, BSc; Huib
van Weelden, MSc; Carla A. F. M. Bruijnzeel-Koomen, MD; Edward F.
Knol, PhD; Willem A. van Vloten, MD; Jon Laman, PhD; Frank R. de
Gruijl, PhD

Arch Dermatol. 2004;140:295-302.

Background Disturbances in UV-induced Langerhans cell migration and
T helper (TH) 2 cell responses could be early steps in the
pathogenesis of PLE.

Objective To establish whether UV-B exposure induces aberrant
cytokine expression in the uninvolved skin of patients with
polymorphous light eruption (PLE).

Design Immunohistochemical staining and comparison of microscopic
sections of skin irradiated with 6 times the minimal dose of UV-B
causing erythema and the unirradiated skin of patients with PLE and
of healthy individuals.

Setting University Medical Center (Dutch National Center for
Photodermatoses).

Patients Patients with PLE (n = 6) with clinically proven
pathological responses to UV-B exposure and normal erythemal
sensitivity. Healthy volunteers (n = 5) were recruited among students
and hospital staff.

Main Outcome Measures Expression of cytokines related to Langerhans
cell migration (interleukin [IL] 1, IL-18,and tumor necrosis factor
[TNF] ); TH2 responses (IL-4 and IL-10); and TH1 responses (IL-6, IL-
12, and interferon ). Double staining was performed for elastase
(neutrophils), tryptase (mast cells), and CD36 (macrophages).

Results The number of cells expressing IL-1 and TNF- was reduced in
the UV-B–exposed skin of patients with PLE compared with the skin of
healthy individuals (P<.05 for TNF-). No differences were observed in
the expression of TH1-related cytokines but fewer cells expressing IL-
4 infiltrated the epidermis of patients with PLE 24 hours after
irradiation (P = .03). After UV exposure TNF-, IL-4, and, to a lesser
extent, IL-10 were predominantly expressed by neutrophils.

Conclusions The reduced expression of TNF-, IL-4, and IL-10 in the
UV-B–irradiated skin of patients with PLE appears largely
attributable to a lack of neutrophils, and is indicative of reduced
Langerhans cell migration and reduced TH2 skewing. An impairment of
these mechanisms underlying UV-B–induced immunosuppression may be
important in the pathogenesis of PLE.

From the Department of Dermatology, University Medical Center
Utrecht, Utrecht (Ms Kölgen, Mr van Weelden, and Drs Bruijnzeel-
Koomen, Knol, and van Vloten); Department of Immunology, Erasmus
Medical Center, Rotterdam (Ms van Meurs and Dr Laman); and Department
of Dermatology, Leiden University Medical Center, Leiden (Ms Jongsma
and Dr de Gruijl), the Netherlands. The authors have no relevant
financial interest in this article.

posted 21 March 2005 22:25               

2000 IU/day have been give to 1 year old child (and kept up for 20 years) with only positive effects being recorded (i.e. 80% drop in diabetes rate).
Source: The Lancet, 2001 Nov 3;358(9292):1500-3.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11705562

This level (2000 IU/day) is being advocated by quite a wide range of sources.

quote:

---

Originally posted by bpeck:
I am posting the following papers in full, because, for people who feel better AVOIDING UV exposure -
it's a little more complicated than just the reduction in vit D formation.

---