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Author Topic: IL-7 May Protect CD4 Cells in HIV  (Read 1955 times)

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Offline Ihavehope

  • Member
  • Posts: 1,366
  • Yes, I'm a cry baby, AND WHAT?
IL-7 May Protect CD4 Cells in HIV
« on: February 08, 2007, 07:26:44 PM »
IL-7 May Protect CD4 Cells in HIV

February 8, 2007

(Reuters Health) - Interleukin (IL)-7 is an attractive candidate for immunotherapy in patients infected with HIV-1, according to investigators at the National Institute of Allergy and Infectious Diseases. Their recent experiments, reported in the online February 5th PNAS Early Edition, also show that IL-7 may be most effective in patients with the greatest degree of immune suppression.
Dr. Paolo Lusso and associates in Bethesda, Maryland, isolated peripheral blood mononuclear cells (PBMCs) from 24 patients at different stages of HIV-1 infection.

To assess apoptosis, they measured annexin V, which preferentially binds to dying cells, and caspase C activation, which occurs during apoptosis. When untreated PBMCs were incubated ex vivo for 7 days, annexin V binding increased dramatically (p < 0.0001).

In contrast, when cells were incubated with IL-7 for 7 days, annexin V binding decreased significantly for up to 6 days, compared with untreated cells (p < 0.0001). During the same period, caspase 3 activation decreased when cells were incubated with IL-7 (p = 0.01).

The investigators observed that the kinetics and magnitude of IL-7's effects varied markedly among patients. Peak reduction in apoptosis ranged from 5.1% to 28.4%, and occurred anywhere between 1 and 6 days. In some samples, the cytokine's effect increased over time, while it decreased in other samples.

Dr. Lusso's group evaluated several demographic, clinical, and immunologic parameters that could have affected IL-7's anti-apoptotic effect. The only factor that played a role was the severity of immune dysfunction; there was a significant inverse correlation between circulating CD4 count and IL-7's efficacy (p = 0.0099).

Similar efficacy was observed when IL-7 was incubated with purified CD4+ and CD8+ cells. IL-7 was equally effective in protecting naďve and memory T cells.

The authors saw no evidence of increased endogenous HIV-1 replication.

"The results of the present study provide a further rationale for consideration of IL-7 as a potential adjuvant therapy in HIV-1-infected individuals in association with antiretroviral therapy," Dr. Lusso and his associates conclude.

Infected: April 2005
12/6/06 - Diagnosed HIV positive
12/19/06 - CD4 = 240  22% VL = 26,300
1/4/07 - CD4 = 200 16% VL = ?
2/9/07 = Started Kaletra/Truvada
3/13/07 = CD4 = 386 22% VL ?

Offline bimazek

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  • Posts: 781
Re: IL-7 May Protect CD4 Cells in HIV
« Reply #1 on: February 08, 2007, 09:42:48 PM »
Interesting post, caused me to want to find out more, is there a substance or molecule that stimulates IL-7?  Lets see what i can find out.

Under IL-7 therapy there are great articles... looks like they are studying adding IL-7 to haart...
this looks like a big thing, but can they make enough IL-7?

some very exciting discoveries in last days and years

monkeys receiving 10 days of IL-7 showed substantial, reversible increases in T-cell numbers involving a dramatic expansion of both naive and nonnaive phenotype CD4+ and CD8+ subsets.

Thus, IL-7 induces dramatic alterations in peripheral T-cell homeostasis in both T-cell-replete and T-cell-depleted nonhuman primates. These results further implicate IL-7 as a promising immunorestorative agent but illustrate that a major component of its immunorestorative capacity reflects effects on mature cells. These results also raise the possibility that IL-7 therapy could be used to temporarily modulate T-cell cycling in vivo in the context of immunotherapies such as vaccination.



IL-7 therapy dramatically alters peripheral T-cell homeostasis in ...
These results also raise the possibility that IL-7 therapy could be used to temporarily modulate T-cell cycling in vivo in the context of immunotherapies ...
www.bloodjournal.org/cgi/content/abstract/101/6/2294

IL-7 therapy dramatically alters peripheral T-cell homeostasis

While IL-7 therapy would never replace current highly active antiretroviral therapy (HAART) for patients, it might help repair the lasting damage that HIV ...
http://www.healthday.com/Article.asp?AID=601624

Natural Immune-System Molecule Helps Shield Against HIV ...
IL-7 could be useful complement to standard therapy, study suggests. ... While IL-7 therapy would never replace current highly active antiretroviral therapy ...

Adjuvant IL-7 or IL-15 overcomes immunodominance and improves ...
Current models of T cell memory implicate a critical role for IL-7 in the effector-to-memory transition, raising the possibility that IL-7 therapy might ...
www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1074679


Clinical trials are already under way in which scientists are boosting HIV-positive patients' IL-7 levels to improve their immune health.

"We desperately need some way of protecting cells from dying in AIDS," said Rowena Johnston, vice president of research at the Foundation for AIDS Research (amfAR) in New York City.

While IL-7 therapy would never replace current highly active antiretroviral therapy (HAART) for patients, it might help repair the lasting damage that HIV inflicts on the immune system, she said.

"Because, even in the first few weeks of infection -- before you even know that you have HIV and haven't started therapy yet -- there is this lasting damage to the immune system that HIV does," Johnston noted. "That is something that absolutely needs to be addressed."

IL-7 is one of a number of interleukin molecules that the body uses as "long-range messengers" to recruit an immune response to sites of injury in the body, explained lead researcher Paolo Lusso. He is an adjunct investigator in the Laboratory of Immunoregulation at NIAID.

According to Lusso, IL-7, especially, is "recognized to be key to the well-being of the T-cell." T-cells are a type of immune system killer cell, as well as a regulatory cell.

very very exciting news here in this article...
http://www.healthday.com/Article.asp?AID=601624

from wikipedia...
Interleukin 7 (IL7) is a hematopoietic growth factor secreted by the Stromal cells of the red marrow capable of stimulating the proliferation of lymphoid progenitors. It is important for proliferation during certain stages of B-cell maturation, T and NK cell survival, development and homeostasis

There are now 33 of these
Interleukins

IL-1 | IL-2 | IL-3 | IL-4 | IL-5 | IL-6 | IL-7 | IL-8 | IL-9 | IL-10 | IL-11 | IL-12 | IL-13 | IL-14 | IL-15 | IL-16 | IL-17 | IL-18 | IL-19 | IL-20 | IL-21 | IL-22 | IL-23 | IL-24 | IL-25 | IL-26 | IL-27 | IL-28 | IL-29 | IL-30 | IL-31 | IL-32 | IL-33
 
all orchestraiting the concert that is the immune system

Growth factor is sometimes used interchangeably among scientists with the term cytokine. Historically, cytokines were associated with hematopoietic (blood forming) cells and immune system cells (e.g., lymphocytes and tissue cells from spleen, thymus, and lymph nodes). For the circulatory system and bone marrow in which cells can occur in a liquid suspension and not bound up in solid tissue, it makes sense for them to communicate by soluble, circulating protein molecules. However, as different lines of research converged, it became clear that some of the same signaling proteins the hematopoietic and immune systems used were also being used by all sorts of other cells and tissues, during development and in the mature organism.

While growth factor implies a positive effect on cell division, cytokine is a neutral term in terms of a molecule's effect on proliferation. In this sense, some cytokines can be growth factors, such as G-CSF and GM-CSF. However, some cytokines have an inhibitory effect on cell growth or proliferation. Yet others, such as Fas ligand are used as "death" signals; they cause target cells to undergo programmed cell death or apoptosis.









this sounds exciting....

Blood, 15 March 2003, Vol. 101, No. 6, pp. 2294-2299

IMMUNOBIOLOGY

IL-7 therapy dramatically alters peripheral T-cell
homeostasis in normal and SIV-infected nonhuman primates

Interleukin-7 (IL-7) is important  in mice and humans because IL-7 receptor alpha  (IL-7Ralpha ) mutations result in a severe combined immunodeficiency phenotype with severe thymic hypoplasia. Recent evidence has indicated that IL-7 also plays an important role as a regulator of T-cell homeostasis.

Here we report the immunologic effects of recombinant human IL-7 (rhIL-7) therapy in normal and simian immunodeficiency virus (SIV)-infected nonhuman primates. Cynomolgus monkeys receiving 10 days of rhIL-7 showed substantial, reversible increases in T-cell numbers involving a dramatic expansion of both naive and nonnaive phenotype CD4+ and CD8+ subsets. Although IL-7 is known to have thymopoietic effects in mice, we observed marked declines in the frequency and absolute number of T-cell receptor excision circle-positive (TREC+) cells in the peripheral blood and dramatic increases in the percentage of cycling T cells in the peripheral blood as measured by Ki-67 expression (baseline less than 5% to approximately 50% after 6 days of therapy) and ex vivo bromodeoxyuridine (BrdU) incorporation. Similarly, moderately CD4- depleted SIV-infected macaques treated with rhIL-7 also had significant increases in peripheral blood CD4+ and CD8+ T cells following rhIL-7 therapy. Thus, rhIL-7 induces dramatic alterations in peripheral T-cell homeostasis in both T-cell-replete and T-cell-depleted nonhuman primates. These results further implicate IL-7 as a promising immunorestorative agent but illustrate that a major component of its immunorestorative capacity reflects effects on mature cells. These results also raise the possibility that IL-7 therapy could be used to temporarily modulate T-cell cycling in vivo in the context of immunotherapies such as vaccination.

monkeys receiving 10 days of rhIL-7 showed substantial, reversible increases in T-cell numbers involving a dramatic expansion of both naive and nonnaive phenotype CD4+ and CD8+ subsets.

Thus, rhIL-7 induces dramatic alterations in peripheral T-cell homeostasis in both T-cell-replete and T-cell-depleted nonhuman primates. These results further implicate IL-7 as a promising immunorestorative agent but illustrate that a major component of its immunorestorative capacity reflects effects on mature cells. These results also raise the possibility that IL-7 therapy could be used to temporarily modulate T-cell cycling in vivo in the context of immunotherapies such as vaccination.

???????? how many people will die before this is added to haart for everyone that needs it now????????  that is my question??  is there enough evidence yet? to use this in wide spread trial?  Do we need to have dialogue with political leaders that if something like this is found that can save many lives in USA, that there is funds to get it to the people suffering??? 







Offline bimazek

  • Member
  • Posts: 781
Re: IL-7 May Protect CD4 Cells in HIV
« Reply #2 on: February 08, 2007, 10:12:34 PM »
Friday, March 18, 2005 
fda mtg on research

More recently, we have been looking at a very interesting finding that again came out of our microarray analysis actually, looking to see which genes were upregulated by HIV and Tat.  And this is the upregulation of the IL-7 receptor alpha chain at the levels of both RNA and protein.
 
  Then this data shows that the newly induct IL-7 receptor is functional.  And it just shows that it phosphorylates or activates STAT-3.  The question arose, okay, we are upregulating the receptor.  But can it do anything?  Maybe it's defective.  But the answer is it does do something.
 
       These are Western blots probed with antibodies to activate its STAT-3.  And you can see that what these have done, these cells are grown.  Then you get rid of all the cytokines, put them in serum-free medium.  Then you blast them with the IL-7 cytokine to look for intracellular signaling.  And when you blast uninfected cells with IL-7 for 20 minutes, you don't get any signaling.  But if they have been HIV-infected, you do get signaling.  These are controls.
 
       Similarly, you see the same thing with Tat treatment.  If there is no Tat treatment, you blast them with IL-7, there is no detectable signaling.  If you blast them with IL-7 and they have been pre-treated with Tat, you get signaling.  So, the upregulated IL-7 receptor was displayed on the surface and it's functional.
 
       This is the data that ties this into a novel positive feedback loop.  And all this says is if you dump IL-7 cytokine into these cultures, you increase the amount of HIV.  And this is a dose response curve with increased amounts of IL-7.  These are physiologic levels.
 
       So, the basic observation is HIV upregulates the IL-7 receptor.  And IL-7 stimulation through the IL-7 receptor upregulates HIV.  So, you have a positive feedback loop.  And just to lead you through that, this is what it looks like presumably.  There is IL-7 cytokine floating around in the supernatant when you are in plasma.
 
       When you infect with the HIV and starting HIV products, one of those is the Tat protein, which feedbacks back, and we believe it stimulates IL-7 receptor transcription.  That gives you IL-7 receptors on the surface, which now signal from the IL-7 cytokine that is kicking around.  And that signaling, we believe, goes back into the nucleus and regulates genes which influence HIV replication.  It may be at the level of entry, we don't know.
 
       So, to give you an idea of where we are going to take this, since the site visit we have actually been awarded a grant to pursue this work and others by the National Institutes of Health.  It's an intramural H targeted antiviral grant.  And part of that is to do mechanistic studies on HIV upregulation by the IL-7 system in these cell types.  And part of it is to study the effects of Nef on primarily human monocytes and macrophages.
 
       The grant is centered around the use of transfection in monocytes, which is a new technique that we have actually developed, and it's giving the potential to do a lot of experiments which haven't been able to be done before in macrophages.  And that will enable us to do the mechanistic studies.
 
       This is just my rogue's gallery of macrophages transfected with yellow fluorescent protein, which you can see is green.  And you get all sorts of things.  You nice stretched out fibroblastic macrophages.  You get some classic fried egg morphology macrophages and small round ones.  So, we are getting a nice transfection.
 
      Just to remind you of the flavivirus biology that we have done.  We have developed dengue virus replicons expressing exogenous genetic material, including HIV proteins.  These are potentially useful for vaccine vectors
     
      the Tat protein is one of the regulatory proteins of HIV-1.  It's a very small protein, about 6 kilodalton.  It is believed to be involved in the progression of HIV infection, the co-factor for Kaposi's sarcoma, and also is involved in the apoptosis of normal cells and in neurological disorders.
     
            The evidence published in the literature shows that high levels of anti-Tat antibody relate to low viral load and seropositive non-progressors.  So, the higher the level of anti-Tat in the body, the slower the disease progression.  It's very well documented now.
     
      So, these studies actually led us to focus our studies to develop a strategy to target the functional domains that are involved in the progression of infection by neutralizing them, and use them as a therapeutic approach, like a therapeutic vaccine.
            www.fda.gov/ohrms/dockets/AC/05/transcripts/2005-4096t2.rtf+%22stimulates+IL-7%22&hl=en&ct=clnk&cd=1&gl=us
           
      Dr. Luke Montaya(?) recently endorsed how useful the therapeutic vaccine could be, as opposed to the preventive vaccine, which none out of 30 are showing any promising results.  So, that gives me really good feedback to focus more on our studies, and confidence to believe what we are doing.  I think that something could be meaningful.
     
            So, Tat, as I mentioned, is a small protein.  So, we mapped the entire Tat protein into multiple domains and figured out the two key domains representing 21-40 amino acid residue, which is cystine rich, and the other one is arginine rich domain, which ranges for 53-68 amino acids.  They are key domains that made pathogenesis.
     
            As you can see, there are multiple cytopathic effects.  Notice when the cells were treated with these two synthetic peptides and then challenged with HIV, the results were quite similar to what we observed with the common and Tat proteins.
     
            In a panel over here we demonstrated not only the recombinant Tat, but these same domains up here, they promoted the formation of new blood vessel formation in the CAM assay, like chicken ellen(?) toy(?) assay.  So, these two domains represent a key domain and are the key target for neutralization in order to slow down the progression of infection.
     
            But before we could use these domains in the form of a therapeutic vaccine, we must modify these domains, because they are pathogenic.  If you don't modify and use them just as is, well they will induce immune response.  Eventually you neutralize those domains.  But before they could do that, they will cause more adverse effect, because they will potentially be given to infected individuals.  And the cells that already are infected will produce more virus.
     
            So, in order to do that, we modify.  We may very selective changes in the side chain of cystine and arginine.  And by this slight modification it completely blocked their pathogenic activity, and yet retained their immunological characteristics.
     
            Since we last had a site visit, we raised antibody in mice, and we got very encouraging results.  We used those antibodies and tested them in the infected assay, and we were able to demonstrate somewhere in the order of 40-70 percent inhibition of HIV application in monocyte by macrophages even in the absence of Tat proteins.
     
            So, we are trying to do now is to use them in -- preferably there is a mouse model available.  We would like to test it out, otherwise we are in collaboration with Dr. Chris Morty(?) in San Antonio, Texas.  We are trying to test their immunological capability in rhesus.
     
            And these are the results which I just said, in one slide.  The modification that we made in the cystine site chain, and also in the arginine over here completely blocked the angiogenesis, as you see clearly in your handout.
     
            So, a summary of the results are the cystine rich and arginine rich Tat sequences, they represent key domains in the HIV Tat protein that made pathogenesis.  Synthetic Tat MPC now multiple MPCs from multiple peptide conjugates, what we did was we used these domains and made a synthetic construct, because this blood type will not be able to raise antibody as it is.
     
            So, in order to increase the size, we used the synthetic backbone of lysine, and then put these domains on top of them, and they were able to induce effective immune response.  So, antibody inhibited induced cytopathic effects.  It's very interesting results.
     
      And selective sites for modification I mentioned.  They completely blocked the functional domain.  And this modification retained large (?) characteristics, but completely blocked their pathogenic effects.
     
            Dr. Dayton's lab that is looking at the molecular biology and gene regulation of HIV in infected primary human macrophages.
     
      Dr. Dhawan is looking at diagnosis and pathogenesis of HIV, focusing on host and viral factors in disease transmission and progression.  And he is also developing diagnostic tools for viral detection.
           
      this seems like good news to me...................
     
      We also wanted to examine whether there was correlation between genotype co-receptor usage and virus replication.  In this study we isolated viruses from patients who were naive and patients on prolonged antiretroviral therapy.  And we have found that actually they continue to use classical chemokine co-receptors CCR5 and CXCR4.  So, there aren't any new receptors that are being used by viruses from patients on antiretroviral therapy.
     
            There might potentially be a switch to co-receptors, to a specific co-receptor.  In this particular case it was switched to CCR5 after they were on prolonged antiretroviral therapy.  And that's not unusual, because that co-receptor usage is associated with less pathogenesis than the CXCR4 using viruses.
     
      Tropism was not apparently related to CD4 count, viral load, genotypic mutation in the whole genes and the C2V3 region, which is actually the major region that dictates the tropism of HIV viruses.  We are now planning some future studies on cytokine regulation, the ability of drug-resistant viruses to cause apoptosis, since we would expect that if they are less pathogenic than naive viruses, they could potentially be less capable of inducing apoptosis.
     
      Andrew Dayton.
     
            The work in my laboratory for many years has been -- at least since I have been at the FDA, has been focused largely on the molecular biology of HIV infection of primary human macrophages.  As many of you know, the macrophage is a central cell in the body involved in the pathogenesis of HIV and the clinical course of AIDS.  It is one of the first cell types to be infected during a transmission.
     
            It is a conduit for bringing HIV across the blood-brain barrier into the brain.  And it serves as a reservoir for virus throughout the clinical course of the disease.  That's largely the reason why I have been focusing on it.  Also, we can study it.  It's a very interesting cell type in that you can have a lot of replication without a lot of cytopathic effect.  So, you can look at what happens to these cells.
     
            Now, most of the work comes from our key project, which has been identification and characterization of macrophage genetic pathways regulated by HIV infection and/or individual HIV genes.  Mostly we have focused on the HIV Tat gene, which is known to affect a large number of cellular genes.
     
      We have gotten into some corollary projects as a result of this.  We have looked at genes that have seemed to be of interest, and they have taken us into related fields which are all relevant.  In particular, we have been looking at the regulation of apoptosis in and also by macrophages.
     
     
       So, the work on apoptosis derived from looking at genes which were regulated by HIV infection.  And a very interesting finding we made is that HIV infection or Tat protein upregulates the expression of TRAIL which is TNF Related Apoptosis Inducing Ligand.  It's a factor which is secreted and causes apoptosis in nearby cells.
     
            And this is of tremendous interest, because TRAIL, which is produced by macrophages, could contribute to bystander mediated apoptosis.  When we did this work it was a theoretical connection.  Shortly therefore in the SKID(?) human-mouse model other investigators actually showed very convincingly that we were having a lot of apoptosis induction in that system by TRAIL and not by direct infection.  So, we were very happy to see the groundbreaking work of ours turned out to have some relevance.
     
            We also found that the HIV infection and Tat upregulate in macrophages at least, Bcl-2, which may contribute to protection of macrophages from apoptosis.
     
            More recently, we have been looking at a very interesting finding that again came out of our microarray analysis actually, looking to see which genes were upregulated by HIV and Tat.  And this is the upregulation of the IL-7 receptor alpha chain at the levels of both RNA and protein.
     
      I'll show you data on this briefly, but what the data is going to say is that the upregulated IL-7 receptor is exposed on the exterior of the plasma membrane.  It is functional, and this upregulation appears to be in a predominant population of macrophages.  I won't actually show you the data for that today.
     
     
     
     

Offline bimazek

  • Member
  • Posts: 781
Re: IL-7 May Protect CD4 Cells in HIV
« Reply #3 on: February 08, 2007, 10:37:32 PM »
i DID A SEARCH ON Interleukin-7 and Vitamin and this is what science has found... seems to me that proper healthy vitamins help the body with IL-7 and with recent discoveries on IL-7

Interleukin-7 Is a Direct Inhibitor of in Vitro Osteoclastogenesis ...
IL-7 also inhibited (P < 0.05) OCL formation in bone marrow cultures that were stimulated with vitamin D3 (10-8 M, 60%), bovine PTH (bPTH) (100 ng/ml, 54%), ...
endo.endojournals.org/cgi/content/abstract/144/8/3524

IL-7—Vitamin D. THE IMMUNOSENESCENCE SCENARIO. Age-related changes of the immune system. (immunosenescence) are directly or indirectly ...

IL7 - interleukin 7
IL-10 regulated in DC the expression of a limited number of genes, including IL-7, the receptors for transferrin and vitamin D(3), structural matrix ...
www.ihop-net.org/UniPub/iHOP/bng/89457.html



Normal myelopoiesis but abnormal T lymphocyte responses in vitamin ...
The vitamin D receptor (VDR) is a transcription factor that mediates the actions of ... Borger P, Kauffman HF, Postma DS, Vellenga E. IL-7 differentially ...
www.pubmedcentral.nih.gov/articlerender.fcgi?artid=150940 - Similar pages

Normal myelopoiesis but abnormal T lymphocyte responses in vitamin ...
File Format: PDF/Adobe Acrobat
types clearly shows that the vitamin D endocrine system ... IL-7 dif-. ferentially modulates the expression of IFN-gamma and IL-4 in activat- ...




Interleukin-7 dose-dependently restores parenteral nutrition-induced gut-associated lymphoid tissue cell loss but does not improve intestinal immunoglobulin a levels.
[My paper] Kazuhiko Fukatsu , Tomoyuki Moriya , Fumie Ikezawa , Yoshinori Maeshima , Jiro Omata , Yoshihisa Yaguchi , Koichi Okamoto , Hidetaka Mochizuki , Hoshio Hiraide , Gil Hardy
BACKGROUND: Without enteral nutrition, the mass and function of gut-associated lymphoid tissue (GALT), a center of systemic mucosal immunity, are reduced. Therefore, new therapeutic methods, designed to preserve mucosal immunity during parenteral nutrition (PN), are needed. Our recent study revealed that exogenous interleukin-7 (IL-7; 1 mug/kg twice a day) restores the GALT cell mass lost during intravenous (IV) PN but does not improve secretory immunoglobulin A (IgA) levels. Herein, we studied the IL-7 dose response to determine the optimal IL-7 dose for recovery of GALT mass and function during IV PN. We hypothesized that a high dose of IL-7 would increase intestinal IgA levels, as well as GALT cell numbers. METHODS: Male mice (n = 42) were randomized to chow, IL-7-0, IL-7-0.1, IL-7-0.33, IL-7-1 and IL-7-3.3 groups and underwent jugular vein catheter insertion. The IL-7 groups were fed a standard PN solution and received IV injections of normal saline (IL-7-0), 0.1, 0.33, 1, or 3.3 mug/kg of IL-7 twice a day. The chow group was fed chow ad libitum. After 5 days of treatment, the entire small intestine was harvested and lymphocytes were isolated from Peyer's patches (PPs), intraepithelial (IE) spaces, and the lamina propria (LP). The lymphocytes were counted and phenotypes determined by flow cytometry (alphabetaTCR, gammadeltaTCR, CD4, CD8, B cell). IgA levels of small intestinal washings were also examined using ELISA (enzyme-linked immunoabsorbent assay). RESULTS: IL-7 dose-dependently increased total lymphocyte numbers in PPs and the LP. The number of lymphocytes harvested from IE spaces reached a plateau at 1 mug/kg of IL-7. There were no significant differences in any phenotype percentages at any GALT sites among the groups. IgA levels of intestinal washings were significantly higher in the chow group than in any of the IL-7 groups, with similar levels in all IL-7 groups. CONCLUSIONS: Exogenous IL-7 dose-dependently reverses PN-induced GALT cell loss, with no major changes in small intestinal IgA levels. IL-7 treatment during PN appears to have beneficial effects on gut immunity, but other therapeutic methods are needed to restore secretory IgA levels.

Daily - Science - 12/31/05
High doses of vitamin D can reduce the risk of developing some common cancers by ... IL-7 is a cytokine--a protein that promotes T-lymphocyte survival and ...
 Vitamin D Can Lower Cancer Risk
High doses of vitamin D can reduce the risk of developing some common cancers by as much as 50%, US scientists claim.
According to BBC News website, researchers reviewed 63 old studies and found that the vitamin could reduce the chances of developing breast, ovarian and colon cancer, and others.
Experts have said that they need to see more research, said BBC correspondent Rachel Wright.
Charities cautiously welcomed the study but warned too much vitamin D could harm the kidneys and liver, she said.
The “natural“ form of the vitamin, called D3, is normally produced in the skin after exposure to sunlight, but is also obtained from certain foods such as oily fish, margarine and meat.
The research, done at the University of California in San Diego, looked at the relationship between blood levels of vitamin D and cancer risk.
Survival rates for Afro-Caribbean people with breast, colon, prostate and ovarian cancers are worse than for white people, possibly because dark skins are not as good at making vitamin D, the researchers said.
The papers reviewed, published worldwide between 1966 and 2004, included 30 investigations of colon cancer, 13 of breast cancer, 26 of prostate cancer and seven of ovarian cancer.
Scientists said analysis showed that, for at least some cancers, the vitamin D factor could not be ignored.
Taking 1,000 international units (IU)--or 25mg--of the vitamin daily could lower an individual’s cancer risk by 50% in colon cancer, and by 30% in breast and ovarian cancer, they said.
The study acknowledged large doses of vitamin D should be treated with caution.
More than 2,000 IU--50mg--a day can lead to the body absorbing too much calcium, possibly damaging the liver and kidneys.
Professor Cedric Garland, who led the review study, said, “A preponderance of evidence, from the best observational studies the medical world has to offer...has led to the conclusion that public health action is needed.“
In the absence of sunshine, a beneficial level of vitamin D could be obtained from a combination of food sources and supplements, he said.
Prof Garland warned that sun exposure had its own concerns.
“Dark-skinned people, however, may need more exposure to produce adequate amounts of vitamin D, and some fair-skinned people shouldn’t try to get any vitamin D from the sun.
“The easiest and most reliable way of getting the appropriate amount is from food and a daily supplement.“





Hardy,G
Herein, we studied the IL-7 dose response to determine the optimal IL-7 dose for ... Vitamin C (ascorbic acid) is oxidised rapidly, especially in the ...
lib.bioinfo.pl/auth:Hardy,G









The vitamin D receptor (VDR) is a transcription factor that mediates the actions of its ligand, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], which can promote monocyte/macrophage differentiation and inhibit proliferation and cytokine production by activated T lymphocytes. In this study, VDR knockout (KO) mice were used to investigate the possible role of VDR in hematopoiesis. The relative number of red and white peripheral blood cells and the percentage of bone marrow macrophages did not differ between VDR KO and wild-type mice. 12-O-tetradecanoylphorbol-13-acetate, but not 1,25(OH)2D3, induced differentiation of bone marrow-committed myeloid stem cells from VDR KO mice to monocytes/macrophages. Production of IL-18, a Th1-promoting cytokine, was reduced in macrophages from these mice. Antigen-stimulated spleen cells from VDR KO mice showed an impaired Th1 cell response and had decreased expression of STAT4, a Th1 cell transcription factor. These results demonstrate the absolute requirement of VDR for 1,25(OH)2D3-induced monocyte/macrophage differentiation but show that monocyte/macrophage differentiation can occur in the absence of this receptor. The observed reduction in Th1 population in these mutant mice may be explained by a loss of macrophage IL-18 production or a suppression of STAT4 expression by activated splenocytes.



Vitamin A Deficiency Multiple Mechanisms Establish a Regulatory ...
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due to the presence or absence of dietary vitamin A. IFN-y,. IL-5,. and IL-7 0 secretion. One hypothesis to explain IFN-y overproduction in hypo- ...





Photoprotection of UV-Irradiated Human Skin: An Antioxidative ...
Sies H, Stahl W: Vitamins E and C, beta-carotene, and other carotenoids as ... IL-10r, TNF-alpha and IL-7 mRNA levels in UV-irradiated human skin in vivo. ...
content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ProduktNr=224194&Ausgabe=228554&am
From our data, we thus finally draw the conclusion that by the combination of antioxidants, such as in the formulation of Seresis, a selective protection of the skin against irradiation can be achieved. This might be important for future recommendations for immediate suppression of the early phase of UV-induced erythema, that means pharmacological prevention of sunburn reaction as well as subsequent chronic skin damage.

I THINK THAT THIS COULD EASILY BE EXTENDED TO INCLUDE THE PROTECTION OF THE GUT FROM OXIDATIVE STRESS IN HIV DISEASE, AND ISNT IT INTERESTING THE IL-7 INVOLVEMENT AND THE SELENIUM 


Endogenous antioxidants are decreased in skin and blood during UV exposure. Combined supplementation of beta-carotene, alpha-tocopherol and ascorbic acid in addition to topical sunscreens may help to lower the risk of sunburning. Acute UV erythema with sunburn reaction are the most important factors in conjunction with the cumulative life-long UV dose for inducing skin damage resulting in photoageing and precancerous and cancerous lesions. Therefore, a clinical, randomized, double-blind, parallel group, placebo-controlled study was conducted in healthy young female volunteers (skin type II) investigating the preventive, photoprotective effect of supplementation with Seresis®, an antioxidative combination containing both lipid and water-soluble compounds: carotenoids (beta-carotene and lycopene), vitamins C and E, selenium and proanthocyanidins. In this study, the oral administration of Seresis appeared to be well tolerated.  From our data, we thus finally draw the conclusion that by the combination of antioxidants, such as in the formulation of Seresis, a selective protection of the skin against irradiation can be achieved. This might be important for future recommendations for immediate suppression of the early phase of UV-induced erythema, that means pharmacological prevention of sunburn reaction as well as subsequent chronic skin damage.




CCR Frontiers in Science | January 2006 | Volume 5
... Distinct Regions of the IL-7 Receptor Regulate Different Bcl-2 Family Members ... Retinoids are natural and synthetic vitamin A derivatives,

Treatment of immune-mediated disorders with active vitamin D ...
Active vitamin D compounds have also been implicated in the treatment of skin ... IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-15, TNF-.alpha., ...


Interleukin-7 and interleukin-15 regulate the expression of the ...
Using the CTCL cell line SeAx as a test system now shows that IL-7 and IL-15 are indeed ... Pathway and Potentiation by Ascorbic Acid (Vitamin C) J. Invest. .



etinoids are natural and synthetic vitamin A derivatives, which regulate development, cell proliferation, and differentiation. Retinoids also act as cancer preventive agents and are presently being used successfully to treat certain types of cancer. Although many studies have shown retinoids to be effective in inhibiting cancer cell growth in vitro and in vivo, the clinical usage of vitamin A derivatives is currently limited by the requirement of relatively large dosages to reach therapeutic efficacy. It is also likely that the responsiveness of cancer cells to retinoids diminishes in relation to malignant progression. Indeed, the growth inhibitory effects of retinoids have been observed in estrogen receptor–positive breast cancer cells of low malignancy, whereas the effectiveness of retinoids has been observed to diminish in highly malignant breast cancer cells that were estrogen receptor–negative. The existing hormonal, chemotherapeutic therapies have provided a substantial improvement for the survival of patients with localized breast cancer; however, treatment for metastatic breast cancer remains palliative. Thus, there is an urgent need to understand the mechanism of retinoid resistance to develop therapeutic agents for metastatic breast cancer.

The physiological actions of retinoids are mediated through two distinct nuclear receptor families, the retinoic acid receptors (RAR α, β, and γ), each of which binds all-trans-retinoic acid or 9-cis-retinoic acid, and the retinoid X receptors (RXR α, β, and γ), which preferentially bind 9-cis-retinoic acid. RARs and RXRs bind to a specific DNA response element (RARE) in the 5′-flanking region of target genes as homodimers or heterodimers, thereby promoting gene transcription.

We studied the loss of retinoid responsiveness from the perspective of subcellular localization of the retinoid receptors. In sharp contrast to RXRα homogeneous nuclear distribution in estrogen receptor–positive HMEC and MCF-7 cancer cells, RXRα localized to the splicing factor compartment (SFC) in estrogen receptor–negative MDA-MB-231 cancer cells. We also found that RXRα localized to the SFC in the connective tissue of invasive breast carcinoma tissue, but not in the epithelial cells. SFC localization was not detected in connective tissues of normal or benign hyperplasia.

Vitamin D receptor B1 (VDRB1), a heterodimerization partner of RXR, is also found in SFC and is redistributed throughout the nucleoplasm upon exposure to its ligand 1,25-dihydroxyvitamin D3. Unlike the ligand-induced dynamic intranuclear mobility of VDRB1, we found that ligand failed to redistribute RXRα from the SFC to the nucleoplasm in MDA-MB-231 cells. This finding allowed us to hypothesize that RXRα might be sequestered in the SFC, thereby contributing to loss of retinoid responsiveness. We demonstrated that RXRα was not localized to active transcription sites in MDA-MB-231 cells but showed extensive colocalization with nascent transcripts in MCF-7 cells. This result was further confirmed by reporter assays when the RXR-selective ligand promoted RXRE (RXR-homodimer target) transactivation in MCF-7 cells but failed to do so in MDA-MB-231 cells. The absence of ligand-dependent transcriptional activation in MDA-MB-231 was not attributable to the reduced RXRα protein expression level because the RXRα level in retinoid-sensitive HMEC cells was the same as that in MDA-MB-231 cells. Thus, we decided to investigate whether altered localization of RXRα could explain the loss of RXRα activity and retinoid responsiveness in the MDA-MB-231 cell line. When MDA-MB-231 cells were infected with adenoviral RXRα, exogenous RXRα was localized throughout the nucleus in addition to the SFC. Nucleoplasmic overexpression of RXRα induced apoptosis in accordance with p21 upregulation and bcl-2 downregulation in the presence of ligand (Figure 1).

 


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