Below is a series of articles showing the critical importance of controlling IL-22. We need ways to boost it for some diseases and ways to turn it down for others. When will drugs be developed for IL 22?
Update on my progress with the sulfa reaction I have been mentioning in last few blogs.
I itch so bad now. Really terrible. Yep the sulfa drug was a mistake. Stuck between a rock and a hard place. I had to try. If I do not, then the infection wins. Worse I continue to expose my son to this horrible resistant and 'rare' bacteria. His immune suppresants would allow the bacteria to grow even faster than it has in me. And it has been pretty agressive in me. Just does not want to die. Started Thanksgiving day after a series of dry Santa Anas. My right nasal passages cracked a little. The the infection came. Was the bacteria in the cat dander I breathed as I brushed the cat? Was it on my skin and in my nasal passages already from some silent colonization of my body that I was not aware of util the bacteria found a way through my skin? just waiting for a chance to grow? Was it my neighbor who sneezed a giant uncovered juioy sneeze ten yards up wind from me--a stong wind. I always move away from neighbors and others outside but I did not see him or hear him until he sneezed. Does it matter how I got the infection or just whether it dies or I do. Itch Itch Itch
Children's Hospital of Pittsburgh
Children's Hospital scientists identify possible target for prevention and treatment of pneumonia
Results of first-of-its-kind research published in the Feb. 10 online edition of Nature Medicine
Researchers at Children’s Hospital of Pittsburgh of UPMC have identified a key protein target that may be a crucial factor in the development of a vaccine to prevent and new therapies to treat pneumonia, the leading killer of children worldwide.
Research led by Jay K. Kolls, MD, chief of the Division of Pediatric Pulmonary Medicine, Allergy and Immunology at Children’s, identified for the first time the importance of a protein known as interleukin 22 (IL-22) in the immune response to a strain of bacterial pneumonia. In the laboratory, the researchers were able to effectively treat mice with pneumonia by using purified IL-22.
Results of the study are published in the February online issue of Nature Medicine.
“Currently there is no vaccine that covers all kinds of pneumonia and antibiotic treatment is sometimes limited by antibiotic resistance. As acute respiratory infections are the no. 1 killer of children in the world, progress in the development of novel vaccines or new, more effective treatments is critical,” said Dr. Kolls, the Neils K. Jerne Professor of Pediatrics and Immunology at the University of Pittsburgh School of Medicine. “Our results raise the possibility of developing new protein-based therapies using IL-22 to limit or prevent pneumonia.”
Pneumonia causes almost one in five deaths in children under age 5 worldwide – more than 2 million children each year, according to the World Health Organization. It kills more children than any other disease – more than AIDS and malaria combined.
IL-22 and interleukin 17A (IL-17A) are produced by a recently discovered lineage of cells known as T Helper Type 17 (Th17). Children’s researchers found evidence that the Th17 cell lineage and its cytokines IL-22 and IL-17A have evolved to promote host defense against certain infections in the lung caused by extracellular pathogens.
This is an important discovery because the Children’s research team proposes that by stimulating the Th17 arm of the immune system, they can more efficiently treat bacterial pneumonia. Furthermore, the researchers propose that Th17 is a less critical pathway for intracellular bacteria such as those that cause listeria and tuberculosis – thus raising the potential to target this pathway in diseases of chronic inflammation such as rheumatoid arthritis or inflammatory bowel disease without increasing susceptibility to these intracellular pathogens.
--Scientists discover cells that control inflammation in chronic disease Clucy.email@example.com
Imperial College London ontact: Lucy Goodchild
A new type of immune cell that can be out of control in certain chronic inflammatory diseases, worsening the symptoms of conditions like psoriasis and asthma, is described for the first time this week in the Journal of Clinical Investigation.
The authors of the study, from Imperial College London, the Istituto Dermopatico dell'Immacolata in Rome and the Center of Allergy and Environment (ZAUM) in Munich, hope their discovery could lead to new treatments for these diseases that would bring the cells under control.
The new cell described in the study, called a Th22 cell, is a kind of T-helper cell. These cells are white blood cells that help to activate other immune cells when the body is infected by a pathogen, such as a virus or bacterium. They also control inflammation in the body to help fight off infection.
According to the new study, Th22 cells play a special role in overseeing and coordinating immune cells that cause inflammation. In chronic and allergic inflammatory diseases like psoriasis and allergic eczema, Th22 cells appear to be malfunctioning, leading to excessive inflammation, which can worsen symptoms.
The researchers hope that it may ultimately be possible to treat chronic skin and possibly also airway diseases by targeting Th22 cells with new drugs.
Dr Carsten Schmidt-Weber, one of the lead authors of the study from the National Heart and Lung Institute at Imperial College London, said: "We are seeing an increase in chronic diseases like skin and airway disease because of changes in people's lifestyles. These diseases can have a big impact on people's lives and patients can face a constant battle to keep their symptoms at bay. We are very excited about discovering this new subset of T-helper cells, as we believe it could provide a new target for the treatment of chronic inflammatory diseases in the future."
The researchers discovered Th22 cells by looking at skin samples from people with psoriasis, atopic eczema and allergic contact dermatitis. They analysed the samples and found a completely new type of cell. The researchers examined the molecules the cells made and found that one of them was a signalling molecule called interleukin-22 (IL-22). This signalling molecule warns tissues that inflammation or infection is going to occur, so the tissues can get ready to recognise and attack pathogens or protect themselves against inflammation. The effect of this can be either protective or detrimental - for example, IL-22 molecules and Th22 cells can cause skin cells to grow too quickly, resulting in painful, flaking skin.
The authors of the new study hope that their new discovery will provide scientists developing treatments for inflammatory disorders with a new cellular drug target. The researchers are now investigating the role of these cells in greater detail and exploring their role in disease progression. In addition, Dr Schmidt-Weber and his colleagues want to know how the cells are generated in the body and whether there is any way to control these cells before they cause unwanted damage.
Gut Instincts: What Harms Some Cells May Protect Against Inflammatory Bowel Disease
19 Dec 2008
In a finding that could lead to improved treatment of chronic inflammatory bowel disease (IBD), Yale University researchers have uncovered a key mechanism in the immune system that appears to offer protection from the disorder. Their work appears in the December 19 issue of Immunity.
IBD is caused by an immune response gone awry. Detecting an inflammatory threat, T helper cells, which boost the body's defense system, overreact. They secrete harmful proteins (cytokines) that destroy the lining of the gastrointestinal tract, causing further inflammation. The Yale team, led by Richard A. Flavell, chair of the Department of Immunobiology, found that the cytokine interleukin-22 (IL-22), which can damage tissue in diseases such as psoriasis, actually seems to play a protective role in the case of inflammatory bowel disease.
"It seems likely that this relates to the type of cell that responds to the IL-22 signal," Flavell said. "Skin cells respond in an inflammatory manner and increase in number - that's psoriasis. In the gut, however, the response to the IL-22 signal is to preserve the life of cells that would otherwise die. IL-22 switches on genes that keep cells alive. We don't yet know why the reaction in the gut is different from that in the skin."
Flavell's team induced colitis in mice and found those that were deficient in interleukin-22 had more severe forms of the disease and higher mortality. In the mice that were protected by IL-22, researchers were surprised to find certain types of white blood cells of the immune system, commonly known as "natural killer cells," acting in ways they had not been known to act.
"Natural killers cells were previously thought to play a role in fighting infection and tumors," Flavell said. "Now, we can see that they also play a role in protecting host tissue from damage caused by an overreacting immune system."
More than half a million Americans suffer from inflammatory bowel disease each year. The most common forms of IBD are Crohn's disease and ulcerative colitis. Treatment most often consists of powerful anti-inflammatory drugs such as prednisone, which can weaken the body's immune response. Severe cases may require bowel resection or permanent colostomy.
Yale scientist Lauren A. Zenewicz, first author of the paper, said the discovery of interleukin-22's protective qualities could lead to treatment for IBD that avoids the side effects of current drug therapies, which can lead to increased susceptibility to disease.
According to Zenewicz, IL-22 only impacts tissues and has no direct effect on the immune response. "This specific targeting will allow us to modulate tissue responses to alleviate tissue destruction during inflammation, while having limited effects on the immune response itself."
Before a new drug treatment based on IL-22 can become reality, however, Zenewicz cautions that more study is needed on its dual nature, to learn why it reacts differently in the context of different diseases. In addition, she said, researchers need to study the impact of a continuous course of IL-22 stimulation. "Gaining a better understanding of both the short-term and long-term effects of IL-22 on different tissues is needed to be able to develop IL-22-related therapeutics," she said.
In addition to Zenewicz, Flavell's team included George D. Yancopolous, David M. Valenzuela, Andrew J. Murphy and Sean Stevens, all of Regeneron Pharmaceuticals, Tarrytown, New York.
Citation: Immunity; Volume: 29; Issue: 6
Contact: Vijay Reddy, MD, PhD
Cell Transplantation Center of Excellence for Aging and Brain Repair
Predicting acute GVHD by gene expression could improve liver stem cell transplant outcomes
Tampa, Fla. (July 21, 2008) – Many cell transplants involve the use of stem cells from another human being (known as an allograft), which raises the major concern of the potential for acute graft-versus-host disease (GVHD). GVHD occurs when an immune response is elicited by the grafted cells against the recipient, resulting in tissue damage for the treated individual.
Presently, there are no definitive markers for predicting the development of acute graft-versus-host disease (GVHD) or its progression following the transplant of allogenic stem cells as therapy for liver cancer.
However, in a study published in the current issue CELL TRANSPLANTATON (17:5), researchers at the University of Florida offer a preliminary "molecular signature" based on gene expression for the development of acute GVHD following allogenic hematopoietic stem cell transplants (HSCT).
Despite immunosuppressive drugs, acute GVHD can develop within 100 days post-transplant. Where tissue damage in the skin, liver and gastrointestinal tract is extensive, prognosis can be poor. Although clinicians can identify a well-defined pathophysiological mechanism for acute graft-versus-host disease (GVHD), being able to uncover molecular markers for a patient's potential to develop GVHD would be a significant breakthrough.
"Our study enrolled four acute GVHD patients and four acute GVHD-free patients and noted significant differences in the expression of 1,658 genes between the control and acute GVHD patients," explained Vijay Reddy, MD, PhD, the study's lead author.
Of the 1,658 genes observed, immune-related genes showed the greatest amount of change.
"We observed a predominately pro-inflammatory gene expression profile in acute GVHD patients, consistent with our knowledge of how GVHD develops," concluded Reddy. "Perhaps the most valuable finding was having discovered the possible role for IL-27, IL-22 and Th17 cellular inflammatory responses in the development of acute GVHD."
Future research, said Reddy and colleagues, may want to address gene expression profiling of acute GVHD immediately after noting clinical symptoms, yet before immunosuppressive drugs are administered.
"Nevertheless, this is an important study to help develop biomarkers for determining who is at risk for GVHD following current and future stem cell treatments," said Dr. Paul Sanberg, Distinguished Professor at University of South Florida Health and coeditor-in-chief of Cell Transplantation.
The editorial offices for CELL TRANSPLANTATION are at the Center of Excellence for Aging and Brain Repair, College of Medicine, the University of South Florida and the Diabetes Research Institute, University of Miami Miller School of Medicine. Contact, Dr. Paul Sanberg at firstname.lastname@example.org or Dr. Camillo Ricordi at email@example.com.