Posted by Angelia-Professional Networkers on March 02, 2004 at 17:09:07:
In Reply to: Crohns disease posted by Anthony on March 02, 2004 at 09:33:07:
If you are the same Anthony that was mentioned at a recent staff meeting, welcome to our marketing family. You were mentioned as someone to watch.
Best wishes as your start your quest to the top!.
I have pasted information that we have in our database on Crohns disease. If you have future questions you can e-mail email@example.com . Angelia
Transfer Factor & Crohn¡¦s Disease
Medical evidence points to the certainty of depressed lymphocyte immunologic competence, in several group studies of Crohn¡¦s disease, which suggests impairment of thymic derived lymphocytes (white blood cells) associated with the diminished numbers of T lymphocytes. This depressed responsiveness results in an overgrowth of bacteria, thus promoting primary infections. This depressed responsiveness was also present in an equal number of patients with ulcerative colitis. Therefore, the most acceptable hypothesis relating to Crohn¡¦s disease, is that it is due to a transmissible agent, one with a long latent period, in a susceptible population, one with an immunological defect.
Considering the findings of clinical studies, it is evident that transfer factors would be of great value in affecting the immune system, in more than one area. In the cases of Crohn¡¦s disease, relating to depressed lymphocyte competence, doctors recommend the use of Transfer Factor„§ along with Transfer Factor Plus„§. The transfer factors will educate the immune system, thus using the inducer factors to locate and destroy harmful bacteria, and the suppressor factors to balance the immune system, so that it does not overreact, therefore blocking harmful autoimmune reactions. Transfer Factor Plus„§ will then educate immature lymphocytes (white blood cells) into mature T-cells, which will then destroy infections.
Two decades ago, a key thymic protein was discovered. ¡§Laboratory studies have indicated that the protein helps activate the immune system in its roles in protecting the body from pathogens including viruses, bacteria, fungi, etc.¡¨ (Health Supplement Retailer, March 1998). This protein programs the T-4 helper cells in the immune system, which in turn find an invading pathogen and tell T-8 killer cells to search and destroy.
Cordyvant, also found in Transfer Factor Plus„§, is a proprietary combination of glyconutrients which support the innate immune system. In addition, glyconutrients activate white blood cells to produce antibodies without the help of T-cells, which is of vital importance in fighting a condition such as Crohn¡¦s disease.
Transfer Factor„§ along with Transfer Factor Plus„§ is suggested to be taken in the following regimen: 1 Transfer Factor Plus„§, twice daily along with 1 Transfer Factor„§, three times per day. Do this for the first 10 days, then increase the Transfer Factor Plus„§ to 2 capsules, twice daily, and Transfer Factor„§ to 2 capsules, 3 times per day. After the 2nd ten days, then triple the above, until the patient is relieved, after which the patient should remain on 1 Transfer Factor Plus„§, twice daily, and 1 Transfer Factor„§, 3 times daily.
Bulletin Board Posts on Crohn¡¦s
We have a lady that got good results with Crohn¡¦s by just taking TF by itself. She is ecstatic after 15 years of suffering. There are more stories on Crohn¡¦s at our website.Go to www.4tf.com/immunity and click on testimonials and then click on "Other" link at the top of the page.
Bob---When I went looking for the post that I have in my files I discovered that this board only goes back to 4/1/01. Don't know where the first quarter of the year is, but I could not find it in the archive index. I will copy most of Charlie Spath's post from 3/1/01. He is talking about an International Diamond who is a walking testimonial about Crohn's disease. Mike could give you his name if you need to reach him directly.
"-----We have an International Diamond who successfully boosted his immune system to control his Crohn's disease by doing the following: He started using Transfer Factor with 3 capsules a day for 3 days, adding one capsule every 3 days, building to 3 capsules 3 times daily for a total of 9 capsules a day. He recommended taking TF 30 minutes before or after meals. Take 4 capsules of Bio EFA with meals, and Digestive Enzymes with Probiotics with meals. He recommended not taking the TF and Digestive Enzymes together, that's why TF before or after meals, not with meals. He also recommended using flaxseed oil on food, eating STEAMED vegetables, NOT raw vegetables. He also suggested using a B12 lozenge.
Hope this helps.
Good advice in the post by Ken. I've also seen good results with two additional products. The powerful multi-source antioxidant, PBGS+, has helped many people with Crohn's and ulcerative colitis. It powerfully assists the body's own healing power. It is our second most important product, next to TF/TF+. Some have also gotten relief with our Aloe Vera Concentrate. Aloe taken internally can be as soothing inside as it is outside.
Hope this helps.
I am currently taking TF for my ulcerative colitis, 3 capsules 3 times a day. I have been on TF for just over a month now and have seen a great improvement in my condition. Should I stay on this protocol or should I also be using TF+ as well. Also, any other 4Life or ShapeRite products that could be helping me? Thanks for your discernment and God Bless!
Steven, delighted to hear that you are doing so well on TF alone. I would stay the course and continue with TF for now and slowly over the next several months, add TF+ at one cap daily for 1-2 weeks and slowly build it to 2, maybe 3 caps daily. I totally agree with William re: Aloe and the anti-oxidants. Good Luck and Stay the Healthier Course.
Greetings Steven from Maine. I think you are right on target although you might want to boost up your TF a little to three three times daily over the next month or two. I would hold on TF+ for the moment unless you are stressed with some bacterial infection. A few with UC have done VERY well with TF alone, so why spend the extra dollars if TF does the trick. Keep us informed about how well you are doing. It is always a blessing for us to hear the good stuff.
God Bless, Dr. David
Clinical Abstracts and Articles on Crohn¡¦s Disease
Gastroenterology 1992 May;102(5):1620-7
Increased interleukin-2 messenger RNA in the intestinal mucosal lesions of Crohn's disease but not ulcerative colitis.
Mullin GE, Lazenby AJ, Harris ML, Bayless TM, James SP.
Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
Crohn's disease (CD) is characterized by granulomatous inflammation of the intestinal mucosa, but the etiology and pathogenesis of the inflammatory lesions are unknown. The aim of this study was to determine whether T-cell activation and lymphokine production occurs in the mucosal lesions of this disease. Total cellular RNA was isolated from peripheral blood lymphocytes and from colonoscopic mucosal biopsies of normal individuals and patients with CD of the colon or ulcerative colitis (UC). Levels of interleukin-2 (IL-2) messenger RNA (mRNA) transcripts in samples were determined using a quantitative reverse transcriptase polymerase chain reaction method. IL-2 mRNA transcripts were detected in histologically normal intestinal mucosal biopsies obtained from control subjects. In CD, higher levels of IL-2 mRNA transcripts were detected in the mucosa from areas of active inflammation, but in areas that were histologically normal, levels were similar to control subjects. The levels of IL-2 mRNA transcripts in biopsies from active and inactive UC were similar to control subjects. Levels of IL-2 mRNA in peripheral blood lymphocytes were low and not significantly different in all groups of subjects. In conclusion, the normal intestinal mucosa contains IL-2 mRNA transcripts and may be an important source of IL-2. Furthermore, the inflammatory lesions of CD, but not UC, have higher levels of IL-2 mRNA transcripts, suggesting that T-cell activation and lymphokine secretion in the intestine may be important in the pathogenesis of CD. These data provide further evidence that the pathogenesis of CD and UC are different.
J Exp Med 1995 Nov 1;182(5):1281-90
Antibodies to interleukin 12 abrogate established experimental colitis in mice.
Neurath MF, Fuss I, Kelsall BL, Stuber E, Strober W.
Mucosal Immunity Section, National Institutes of Health/National Institute of Allergy and Infectious Diseases/LCI, Bethesda, Maryland 20892-1890, USA.
In this study, we describe a novel murine model of chronic intestinal inflammation induced by the hapten reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS). Rectal application of low doses of TNBS in BALB/c and SJL/J mice resulted in a chronic transmural colitis with severe diarrhea, weight loss, and rectal prolapse, an illness that mimics some characteristics of Crohn's disease in humans. The colon of TNBS-treated mice on day 7 was marked by infiltration of CD4+ T cells; furthermore, in situ polymerase chain reaction studies revealed high levels of interferon (IFN)-gamma mRNA in diseased colons. Isolated lamina propria (LP) CD4+ T cells from TNBS-treated mice stimulated with anti-CD3 and anti-CD28 antibodies exhibited a Th1 pattern of cytokine secretion: a 20-50-fold increase in IL-2 and IFN-gamma levels and a 5-fold decrease in IL-4 levels as compared with those of stimulated LP CD4+ T cells from control BALB/c mice. Administration of monoclonal anti-IL-12 antibodies to the TNBS-treated mice both early (at 5 d) and late (at 20 d) after induction of colitis led to a striking improvement in both the clinical and histopathological aspects of the disease and frequently abrogated the established colitis completely. Furthermore, LP CD4+ T cells isolated from anti-IL-12-treated mice failed to secrete IFN-gamma upon in vitro stimulation. In summary, the data demonstrate the pivotal role of IL-12 and IFN-gamma in a TNBS-induced murine model of chronic intestinal inflammation. Furthermore, they suggest the potential utility of anti-IL-12 antibodies in patients with Crohn's disease.
IMMUNE WARS: NEW BATTLES ON AN OLD FRONTIER
In the best of all worlds, the immune system serves as our front line of defense, fighting off disease right and left. But when this system misfires, the body turns against itself, wreaking inflammation and havoc. Recent advances in immunologic research, now being applied to inflammatory bowel disease (IBD), suggest a growing connection between the skirmishes within the immune system and the suffering of people with Crohn's disease and ulcerative colitis. Armed with this newfound knowledge of immunology, as well as new therapies, IBD physicians are negotiating a cease-fire.
For years, researchers have assumed that a link exists between IBD and the immune system. People with IBD often develop inflammatory diseases of the eye, joints, skin, and liver--extraintestinal complications that are thought to involve immune mechanisms. Also, IBD responds to corticosteroids, anti-inflammatory agents that are commonly prescribed for immune disorders.
The importance of this connection is increasing, however, with recent research findings in the field of immunology. "The development of animal models, as well as advances made at a basic science level by immunologists, molecular biologists, and biochemists--those advances are now being applied to IBD," says Richard P. MacDermott, MD, chief of the Gastroenterology Section at the Lahey Clinic in Burlington, Mass.
"AIDS research has helped," adds R. Balfour Sartor, MD, chairperson of CCFA's National Scientific Advisory Committee. "A huge amount of work has been done on the T cell because of AIDS." Thanks to these advances, Sartor and other scientists have developed a new theory on the connection between the immune system and IBD.
A State of Tolerance
The immune system comprises cells that recognize and destroy antigens, foreign substances that enter the body. These antigens can be bacteria, viruses, fungi, or parasites. When an antigen attacks, the cells of the immune system rally to respond. These white blood cells include lymphocytes, monocytes, macrophages, granulocytes, and mast cells. Lymphocytes are the primary officers of the immune defense. They are produced by the organs of the immune system, which include the bone marrow, the thymus gland in the neck, the spleen, and the intestine known as Peyer's patches).
To defend the body, these immune system cells migrate to the antigen's location. The affected area becomes red, painful, and swollen, and the surrounding blood vessels congested. Lymphocytes secrete chemicals known as cytokines, which circulate throughout the blood to attract more cells to the scene of the crime.
The most active lymphocyte is the T cell, so named because it develops in the thymus. T helper 1 (Th1) cells, one type of T cell, and macrophages help to promote inflammation by producing pro-inflammatory cytokines. These chemicals include interleukin-1 (IL-1), IL-12, tumor necrosis factor-alpha (TNF-alpha), and gamma interferon (IFN-gamma)--all of which incite inflammation.
T helper 2 (Th2) cells, another type of T cell, and macrophages produce anti-inflammatory cytokines, which include IL-4, IL-10, transforming growth factor-beta (TGF-beta), and IL-1 receptor antagonist (IL-1ra). These chemicals serve to calm down the inflammatory response after the offending antigen has been destroyed.
The intestine is a major player in this defense force; most lymphocytes are produced here. "The primary mechanism of the intestine is to recognize and respond to potential antigens, and yet not respond to normal bacteria," says Dr. Sartor. "Normal" bacteria, or resident enteric microflora, are the approximately 1 billion to 1 trillion bacteria that exist in every gram of intestinal contents. The intestine doesn't normally respond to these bacteria, but responds adequately to invading antigens -- an immunologic state is known as tolerance.
In IBD, according to the latest hypothesis, the immune system's tolerance of enteric microflora falters. "The immune process is a defense mechanism against infection," says Dr. MacDermott. "In Crohn's disease and ulcerative colitis, this process is activated by intestinal bacteria and doesn't turn off." Therefore, people with IBD suffer the symptoms of an inflammation of the intestine--fatigue, loss of appetite, weight loss, diarrhea, bleeding, and cramps. Dr. Sartor adds that it makes sense that this lack of tolerance would occur mostly in the lower intestine, where there are about 1 million more times bacteria as in the upper gastrointestinal tract.
Why do some people lack the ability to regulate tolerance, and others don't? "That's where genetic factors play a role," notes Dr. MacDermott. Researchers are trying to find out if certain people are genetically predisposed to an overly eager immune system.
The rodent models used by scientists to help investigate the connection between immunology and IBD have been pretty important players in this scientific drama. Rats and mice are ideal candidates for immunology research, because their immune system is well understood, and closely resembles that of humans. Many models were developed by immunologists not involved in IBD, thus bringing the best immunologic researchers into the mix.
One mouse model that has greatly benefited IBD research is the "transgenic rat," in which the human gene HLA-B27 is inserted into the eggs of female rats. Previous studies have associated HLA-B27 with inflammatory diseases in humans, and sure enough, these rats develop inflammation of the colon, gastritis, and arthritis. "When these rats are raised in a germ-free environment, without bacteria in the intestine, they do not develop intestinal or joint inflammation," notes Dr. MacDermott. "When HLA-B27 rats are given bacteria--particularly Bacteroides, which are normally present in the colon--they develop chronic inflammation of the intestine or joints." This supports the role of enteric microflora in the development of disease.
Knockout mice, another rodent model used in immunology, are mice in which the genes for certain cytokines, such as IL-10, are deleted, or "knocked out." "If you delete IL-10, the animal develops colitis," notes Dr. Sartor. "But investigators have shown that if you add IL-10 into the system before the mice become ill (at three weeks of age), colitis can be prevented. Also, these mice do not develop coliis in a bacteria-free environment."
Sartor explains that this holds true for other anti-inflammatory cytokines as well. "If you knock out anti-inflammatory cytokines such as TGF-beta, IL-10, and IL-1ra, you get a more aggressive inflammatory response. Whereas, if you block IL-1, TNF-alpha, and IL-12, you can prevent colitis."
Science Strikes Back
Researchers are tapping into this inflammatory action now, applying this basic scientific research to humans. They are developing therapies from anti-inflammatory cytokines, as well as antibodies that squelch the efforts of pro-inflammatory cytokines. Although agents that have been produced previously, such as azathioprine, cyclosporine, 6-mercaptopurine (6-MP), and methotrexate, have been used to suppress the overreacting immune system, these can cause various side effects. Furthermore, in the case of 6-MP, positive results take several months to occur. Finally, the older therapies suppress the entire immune system, while the new treatments target specific components of the immune system.
Of the newer therapies, anti-TNF-alpha--an antibody against TNF-alpha--is causing the most excitement in the community of IBD researchers. Centocor, Inc. is manufacturing this therapy under the name cA2. The company recently reported significant success in two multicenter trials of people with moderate to severe Crohn's disease and enterocutaneous fistulas (abnormal channels that connects the gut to the skin or to another organ) associated with Crohn's disease. Celltech, another company, also reported success this year with CDP571, a different antibody to TNF-alpha.
"Studies have involved patients with very severe disease who are resistant to other treatments," says Stephan R. Targan, MD, Director of the IBD Center at Cedars-Sinai Hospital in Los Angeles. "Single outpatient intravenous infusions of anti-TNF-alpha have resulted in a dramatic response, remissions that persist for long periods of time with minor side effects."
Dr. Targan suggests a reason for this success. "In some studies in animal models, TNF-alpha seems to be the central molecule of the inflammatory response," he points out. "It does more than cause inflammation: It turns up the temperature of other cells, because it is involved in the production of other pro-inflammatory cytokines such as IFN-gamma. Anti-TNF-alpha seems to re-set the temperature of the disease, 'the immunostat,' by preventing cells in the mucosa [intestinal lining] from producing IFN-gamma."
One-third of patients involved in studies so far, however, have not responded to anti-TNF. "These people may have a different type of inflammation in the mucosa," says Dr. Targan. "One type of patient has more cells that produce IFN-gamma, and may benefit from anti-TNF, and patients that have no IFN-gamma don't benefit at all." Preliminary data is leading researchers to think that there are two distinct types of Crohn's disease, one that responds to anti-TNF-alpha and one that does not respond. Eventually, they hope to be able to predict who will or will not respond, based on gene markers.
Although anti-TNF appears promising, its long-term effects have yet to be determined. To this end, Centocor and Celltech are beginning additional clinical trials this year. Meanwhile, Centocor is filing an application for FDA approval of cA2 for the treatment of Crohn's disease later this year.
Another therapy that shows some promise is IL-10. Infusions of this anti-inflammatory cytokine have been shown to prevent inflammation in rat and mouse models of colitis. Studies in humans with IBD have demonstrated success in reducing disease, but have involved small populations. A larger, multicenter trial has been undertaken by Schering-Plough Corporation, involving 300 people whose Crohn's disease has not responded to treatment with steroids.
Antisense drugs take a different path in reducing inflammation, by altering the genetic messages encoded in our cells. One such agent targets intercellular adhesion molecule 1 (ICAM-1), which boosts and prolongs the inflammatory reaction by recruiting cells from the circulation to the site of inflammation. By blocking the strand, or "sense," of messenger RNA that issues instructions to ICAM-1, the antisense drug deactivates this harmful molecule.
In a recent trial of antisense therapy conducted by Isis Pharmaceuticals--the first study to show this agent's effectiveness in humans--seven of 20 Crohn's disease patients achieved remission. To ascertain whether the preliminary results of this small study will hold for a larger population, Isis is currently conducting a 300-patient multicenter study. Participants have moderately active, steroid-dependent Crohn's disease.
Although these immunosuppressive therapies are showing some promising results, they are expensive prospects: They are biologic, derived from living organisms, not synthetic agents. "Biologics are not cheap, because they require high-tech recombinant [from different organisms] material," explains Dr. Sartor. "We need to decide how to best use these therapies." Researchers are recommending that carefully designed trials consider long-term effectiveness, safety, quality of life, and cost outcomes when comparing these newer therapies with standard ones.
CCFA on the New Frontier
There is no doubt of the involvement of the immune system in Crohn's disease and ulcerative colitis, but the questions of how and why remain open. "There is general agreement on the dysfunction of the immune system," says Dr. Sartor. "It's responding where it should not be responding. Many believe the intestinal bacteria theory, but there are other hypotheses--that the mucous membrane of the colon allows bacteria to cross into the colon, or that there is a virus causing the immune response."
These questions only will be answered by research, and then more research. CCFA has been involved in immunologic research since its inception, and has played a pivotal role in funding scientific investigations. And this support continues--most of the current CCFA grants are related to immunology, enabling investigators to determine the roles of the many components of the immune system. Does TNF-alpha stop the intestine from healing? Do epithelial cells--cells that line the intestine--participate in the immune response? Does the immune system respond to specific types of intestinal bacteria?
Investigators also are trying to determine the genetics end of the immunology question. "There is little doubt that genetics influences the immune system," says Dr. Sartor. "There may be defects in the specific genes that play a role in the immune system." In line with this theory, researchers are looking for the genetic signals that regulate the various immune system players.
The mass of information gathered by researchers is facilitating the next step--trials of new therapies. "This also is where CCFA comes in. The foundation is playing a key role in the effort to translate basic science studies to trials of new drug therapies and patients," says Dr. MacDermott. CCFA is working in partnership with pharmaceutical companies to recruit patients for important clinical trials and is establishing a national network of clinical investigators. Experimental therapies that target the immune system are showing significant promise, but new clinical trials are necessary to prove that these therapies can live up to this promise--safely and effectively.
Although more research is yet to be done, investigators appear to be winning preliminary battles on this new frontier--some small steps toward the giant leap of finding the cause of and cure for IBD.
--SARA M. SILBERMAN
Staff Writer, CCFA
MONOCLONAL ANTIBODY THERAPY FOR CROHN'S DISEASE
Researchers have been keenly interested in the role of inflammatory cytokines in patients with Crohn's disease. These inflammatory substances may play a role in perpetuating the inflammation of Crohn's disease. As a result, there has been great interest in designing drugs which target and neutralize the cytokines.
Recent clinical studies using these drugs are showing promising results. Antibodies, the foot soldiers of the immune system, can be designed to stick to specific immune cells and substances. These monoclonal antibodies are genetically engineered to adhere to and neutralize certain cell surface components or inflammatory cytokines.
Many studies point to the cytokine tumor necrosis factor-alpha (TNF-alpha) as a key player in mediating the inflammation of Crohn's. TNF-alpha is increased in the bowel lining of patients with inflammatory bowel disease and plays a role in activating the inflammation producing T-cells in patients with Crohn's. Monoclonal antibodies that neutralized TNF-alpha have shown promise in other inflammatory conditions such as rheumatoid arthritis.
An uncontrolled 1995 study reported that eight out of ten patients with Crohn's disease who had not responded to conventional therapy went into a remission after receiving a single infusion of an anti-TNF-alpha monoclonal antibody called cA2. These results prompted researchers to conduct a double-blind, placebo-controlled study using a different type of monoclonal antibody to TNF-alpha called CDP571. The results were reported in the February 22, 1997 issue of The Lancet.
The trial evaluated 31 patients who were on azathioprine for greater than one month, a stable dose of 5-ASA drugs for at least one week and less than 10mg of prednisolone at a stable dose for greater than two weeks and whose disease remained active. Eligible patients received either the monoclonal antibody CDP571 at 5mg/kg or placebo infused over 60 minutes. After the infusion, the patients were seen regularly over an eight week period and their disease activity was monitored.
Results of the Trial
The disease activity of the group receiving the monoclonal antibody CDP571 dropped significantly within two weeks of the infusion. Nine patients who received the infusion achieved remission or near remission at the two week follow-up after the infusion. In the placebo group, the median disease activity scores didn't change significantly and none of the placebo patients were in remission at two weeks.
The patients tolerated the infusion very well. No serious adverse effects were seen. While five of the 21 patients who received CDP571 reported mild side effects on the day of infusion (e.g.. dizziness, abdominal pain), four of ten who received placebo had similar symptoms.
Who Should Get Anti-TNF-alpha Antibodies?
Several reports have confirmed the effectiveness of monoclonal antibodies to TNF-alpha for patients with Crohn's disease. So far, the trials have been limited to patients who have failed current conventional therapy. When these medicines become widely available patients who have failed conventional therapies will be the best candidates for treatment. The results have been quite encouraging, few side effects have been seen and improvement has been seen in most patients after one infusion (sometimes lasting up to three months). None of these drugs are currently available for use outside a clinical research trial. There is no data regarding the long-term use of these medicines.
Several other 'biological" designer drugs are now being studied as treatments for patients with Crohn's disease and ulcerative colitis such as interleukin-10. These treatments are showing great promise and will likely, in the near future, be invaluable adjuncts to current therapies.
James F. Marion, M.D.
Clinical Instructor of Medicine
Mount Sinai School of Medicine
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