Antiretroviral Drugs May Protect Against Sexual Transmission Of HIV

Daily Science Journal (Feb. 12, 2008) — A new study in macaques suggests that antiretroviral drugs used to treat HIV could also protect people from getting the AIDS virus, especially if two drugs are taken in combination before exposure to the virus occurs.

A new study in macaques suggests that antiretroviral drugs used to treat HIV could also protect people from getting the AIDS virus, especially if two drugs are taken in combination before exposure to the virus occurs. (Credit: iStockphoto/Claire George)

The study found that macaques which were repeatedly exposed to SHIV (a virus closely related to HIV) but received antiretroviral drugs were less likely to become infected than exposed macaques that received no anti-HIV medication. The best protection was seen in macaques that had received a combination of two drugs. The study, led by José Gerardo García-Lerma and Walid Heneine from the US Centers for Disease Control and Prevention, is the culmination of a series of experiments designed to show how similar studies in humans -- some of which are planned and in progress -- can be optimally designed.

Although HIV treatment has rapidly advanced since the introduction of antiretroviral drugs in the 1990s, the absence of an effective vaccine means the virus continues to spread, infecting 2.5 million people each year. Pre-exposure prophylaxis (PrEP) -- the prevention of infection by treating people with drugs before they are exposed to the germ in question -- is often used to prevent malaria, but has not yet been shown to be effective against sexual transmission of HIV.

To simulate a common route of HIV transmission in humans, the researchers exposed the macaques to low weekly doses of SHIV that were given rectally. Five groups of macaques were all exposed to the virus in the same way, but they were given different dosages and combinations of antiretroviral drugs. Three groups received drugs daily: the first was only injected with one anti-HIV drug, emtricitabine (FTC); the second group received a daily dose of this drug by mouth in combination with an oral form of another anti-HIV drug called tenofovir; the third was injected with FTC and a high dose of tenofovir every day. A fourth group was also injected with FTC and a high dose of tenofovir, but macaques in this group were only treated shortly before and after the weekly exposures to HIV. For comparison a fifth group of macaques received no anti-HIV drugs.

The results showed that macaques from any of the four groups that received drugs were less likely to become infected than those in the fifth (control) group. All of the macaques receiving the combination of both FTC and the high dosage of tenofovir were protected from infection -- whether they were from the group that received these drugs daily, or only around the time of exposure to infection. The results suggest that higher doses and combinations of drugs worked better than single or low doses, and also that PrEP may not need to be taken every day to be effective.

The researchers also observed some risks that emphasize the need for careful design of human PrEP studies. They found some viral resistance to one of the drugs, FTC, in macaques that became infected. In addition, doses of tenofovir that resulted in maximum protection for macaques are higher than would be safe in humans.

In a related perspective article, Myron Cohen and Angela Kashuba from the University of North Carolina (Chapel Hill, NC, USA), uninvolved with the study, note that the results "highlight an exciting and potentially important use" of antiretroviral drugs to prevent sexual transmission of HIV.

Journal citation: García-Lerma JG, Otten RA, Qari SH, Jackson E, Cong M, et al. (2008) Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PLoS Med 5(2): e28. doi:10.1371/journal.pmed.0050028 http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050028

Adapted from materials provided by Public Library of Science, via EurekAlert!, a service of AAAS.

Read the rest of this entry »

Herpes Medication Does Not Reduce Risk Of HIV Infection In Individuals With HSV-2, Study Finds

Daily Science Journal (Feb. 10, 2008) — An international clinical trial has found that acyclovir, a common medication for treating herpes simplex virus-2 (HSV-2), the most common cause of genital herpes, does not reduce the risk of HIV infection when taken by people infected with HSV-2. Multiple studies have shown that people with HSV-2 have a higher risk of acquiring HIV. Researchers had hoped that acyclovir's ability to suppress the herpes virus, and its associated genital sores and breaks in the skin, could cut down on the likelihood of HIV being transmitted to a person with HSV-2 during sexual intercourse.

The Phase III clinical trial was led by the University of Washington in Seattle, in coordination with the HIV Prevention Trials Network, an international consortium funded by the National Institute of Allergy and Infectious Diseases (NIAID) in the National Institutes of Health. The findings were presented this week at the Conference on Retroviruses and Opportunistic Infections in Boston.

"The study was successful in answering the question of whether acyclovir could cut down on the risk of HIV acquisition for people infected with HSV-2," explained Dr. Connie Celum, the leader of the study and a UW professor of global health and medicine in the Division of Allergy and Infectious Disease and director of the International Clinical Research Center in the UW Department of Global Health. "We were hopeful that acyclovir would help reduce HIV acquisition in people with HSV-2. Though the study did not find that acyclovir helped with HIV acquisition, we did find that it reduced genital ulcers associated with HSV-2. Now we need to continue our research on the mechanisms through which HSV-2 acts as a risk factor for HIV, and how we might be able to use that knowledge to reduce the spread of HIV."

HSV-2 is one of the most common sexually transmitted infections worldwide and is especially prevalent in areas with high rates of HIV infection. Most people who are infected with HSV-2 do not know they have the virus because symptoms can be mild or absent. In some infected individuals, the virus can produce recurring genital herpes, a condition characterized by sores and breaks in the skin of the genital region. An active HSV-2 infection also attracts immune-system cells called CD-4 T-cells to the genital region, and HIV easily attaches to this type of cell. Multiple studies have shown that people with HSV-2 have a two-fold increase in their risk of acquiring HIV.

This study followed up on those results to test the theory that suppressing HSV-2 could cut down on HIV acquisition. It was launched in 2003, and with nine study sites in Peru, South Africa, Zambia, Zimbabwe, and the United States, it was the largest study yet of herpes suppression. There were 3,277 people with HSV-2 initially enrolled in the study, 105 people excluded, and 3,172 people included in the final analysis. Volunteers in Peru and the United States were HSV-2-infected men who have sex with men, and volunteers in Africa were HSV-2-infected women.

Half of the participants were randomly assigned to receive either a placebo or a standard daily dose of acyclovir, 400 mg twice a day. The study was double-blinded, meaning that neither participants nor care providers knew which treatment the participants were receiving. Both the placebo and treatment groups received standard HIV-prevention treatment, which includes being supplied with condoms and given extensive counseling on how to reduce the risk of HIV infection.

Researchers found that there was a 3.9 percent HIV incidence rate, a total of 75 cases, in participants who received acyclovir suppression, and a 3.3 percent HIV incidence rate, or 64 cases, in the placebo group. The difference between the groups was not statistically significant. The acyclovir treatment did succeed in reducing genital ulcers -- participants in the treatment group had a 37 percent reduction in genital ulcer incidence, and a significantly lower proportion of ulcers due to HSV-2.

"The study answered the scientific questions it was designed to answer," says Dr. Anna Wald, a UW professor of medicine and epidemiology who also helped lead the study. "The sites were able to recruit and retain a large number of volunteers, who maintained a high level of adherence to the twice-daily drug regimen. While we are disappointed with the results, the study was well-conducted and provides a clear answer about using acyclovir to reduce the risk of becoming HIV-infected."

The study participants have been informed of the findings and are being counseled on the continued need to avoid HIV exposure. Volunteers who became infected with HIV during the trial have been referred for appropriate medical care and treatment.

The study was supported by NIAID, and the acyclovir was supplied by GlaxoSmithKline. The HIV Prevention Trials Network is led by Family Health International, the network laboratory of Johns Hopkins University, and the Statistical Center for HIV/AIDS Research and Prevention at the Fred Hutchinson Cancer Research Center in Seattle. The study was conducted at the following sites: Iquitos, Lima and Pucallpa, in Peru; Johannesburg, South Africa; New York, San Francisco, and Seattle, in the United States; Lusaka, Zambia; and Harare, Zimbabwe.

Adapted from materials provided by University Of Washington.

Read the rest of this entry »

Giving Mice A Cold Virus Offers Hope Of New Asthma Treatments

Daily Science Journal (Feb. 8, 2008) — Scientists have been able to recreate rhinovirus infection, which is behind most common colds, in a small animal for the first time. For fifty years since they were discovered, it had been thought that rhinoviruses could only infect humans and chimpanzees. But now a team of scientists led by Professor Sebastian Johnston at the MRC/Asthma UK Centre in Allergic Mechanisms of Asthma at Imperial College London, has been able to infect mice with rhinoviruses.

Scientists have been able to recreate rhinovirus infection, which is behind most common colds, in a small animal for the first time. For fifty years since they were discovered, it had been thought that rhinoviruses could only infect humans and chimpanzees. (Credit: iStockphoto/Jennifer Sheets)

Rhinoviruses are an unwelcome inconvenience for the majority of the population as they cause around three quarters of common colds. However they can also have serious consequences. In susceptible people, they can be fatal. They can lead to the hospitalisation of infants, pneumonia in people with weakened immune systems and they trigger most asthma attacks. They are also the major cause of acute attacks of COPD (chronic bronchitis and emphysema), and are thus the major killer in these diseases.

Professor Johnston said: “Until now it has not been possible to study rhinovirus infection in small animals. This has been a major obstacle to developing new treatments and there is currently no effective treatment for rhinovirus infection.”

It had been thought that mice and other small animals were resistant to rhinoviruses. Of the 100 known strains of rhinovirus, 90 per cent use a binding molecule, called ICAM-1 that is found on the surface of human cells, as their receptor. But the viruses are unable to bind to the mouse version of this receptor.

Professor Johnston explained: "We previously found that once inside the mouse cell a rhinovirus reproduces itself as well as it does in human cells. But the virus couldn’t infect the mouse cell because the receptor (acting like a door key) couldn’t get into the cell.

“Now we’ve modified the mouse receptor so it is more like a human one. This means the virus can infect the cells of these modified mice.”

Professor Johnston added: "We found that mice with the modified receptor were susceptible to infection with a rhinovirus. If combined with an allergen (ovalbumin which is found in egg white) that could cause an allergic reaction in the lungs, the virus could make the response worse and lead to an 'asthma attack'."

The team was able to observe that when the virus was combined with an allergic reaction, the mouse responded similarly to humans. This means it provides a good model for the study of severe asthma attacks.

"These mouse models should provide a major boost to research efforts to develop new treatments for the common cold, as well as for more potentially fatal illnesses such as acute attacks of asthma and of COPD."

The chief executive of the Medical Research Council, Sir Leszek Borysiewicz said: “This important and fundamental discovery will enable us to understand the effects rhinoviruses and common colds have on our health. It will open up new paths to finding treatments which have been delayed for many years and provides us with the opportunities for further breakthroughs in the future.”

Leanne Male, Assistant Director of Research at Asthma UK commented: "Ninety per cent of people with asthma tell us that colds and flu triggers their asthma symptoms but as yet there is no specific treatment for virally induced asthma attacks and steroid treatments are only partially effective against them. We welcome this latest advancement as it will lead to a greater understanding of viral infections and their link with asthma and may help the development of a suitable treatment for virus-induced asthma attacks, thus greatly improving the lives of the 5.2 million people with the condition in the UK."

Journal article: Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Published online in Nature Medicine.

The research was funded by the Medical Research Council, Asthma UK and GlaxoSmithKline.

Adapted from materials provided by Imperial College London.

Read the rest of this entry »

Virtual Human In HIV Drug Simulation

Daily Science Journal (Feb. 2, 2008) — The combined supercomputing power of the UK and US ‘national grids’ has enabled UCL (University College London) scientists to simulate the efficacy of an HIV drug in blocking a key protein used by the lethal virus. The method – an early example of the Virtual Physiological Human in action – could one day be used to tailor personal drug treatments, for example for HIV patients developing resistance to their drugs.

The study ran a large number of simulations to predict how strongly the drug saquinavir would bind to three resistant mutants of HIV-1 protease, a protein produced by the virus to propagate itself. These protease mutations are associated with the disease’s resistance to saquinavir, an HIV-inhibitor drug.

The study, by Professor Peter Coveney and colleagues at the UCL Department of Chemistry, involved a sequence of simulation steps, performed across several supercomputers on the UK’s National Grid Service and the US TeraGrid, which took two weeks and used computational power roughly equivalent to that needed to perform a long-range weather forecast.

The idea behind the Virtual Physiological Human (VPH) is to link networks of computers across the world to simulate the internal workings of the human body. The VPH – mainly a research initiative at present – allows scientists to simulate the effects of a drug and see what is happening at the organ, tissue, cell and molecular level.

Although nine drugs are currently available to inhibit HIV-1 protease, doctors have no way of matching a drug to the unique profile of the virus as it mutates in each patient. Instead, they prescribe a course of drugs and then test whether these are working by analysing the patient’s immune response. One of the goals of VPH is for such ‘trial and error’ methods to eventually be replaced by patient-specific treatments tailored to a person’s unique genotype.

Professor Peter Coveney says: “This study represents a first step towards the ultimate goal of ‘on-demand’ medical computing, where doctors could one day ‘borrow’ supercomputing time from the national grid to make critical decisions on life-saving treatments.

“For example, for an HIV patient, a doctor could perform an assay to establish the patient’s genotype and then rank the available drugs’ efficacy against that patient’s profile based on a rapid set of large-scale simulations, enabling the doctor to tailor the treatment accordingly.

“We have some difficult questions ahead of us, such as how much of our computing resources could be devoted to helping patients and at what price. At present, such simulations – requiring a substantial amount of computing power – might prove costly for the National Health Service, but technological advances and those in the economics of computing would bring costs down.”

For the moment, Professor Coveney’s group is continuing to look at all the protease inhibitors in a similar way. The VPH initiative, now underway with 72 million euros of initial funding from the EU, will boost collaboration between clinicians and scientists to explore the scope for patient-specific medical treatments based on modern modelling and simulation methods.

Journal reference: ‘Rapid and Accurate Prediction of Binding Free Energies for Saquinavir-Bound HIV-1 Proteases’, by Ileana Stoica, S. Kashif Sadiq, and Peter V. Coveney, is published online in the Journal of the American Chemical Society on Tuesday 29 January 2008.

The study was partially funded by the EPSRC, the EU-supported ViroLab project and the National Science Foundation. The UK National Grid Service also provided access to their resources and support for this project.

Adapted from materials provided by University College London.

Read the rest of this entry »

How Poxviruses Such As Smallpox Evade The Immune System

Daily Science Journal (Feb. 1, 2008) — Scientists at Saint Louis University and the University of Alabama at Birmingham have uncovered important new information about a key protein that allows viruses such as smallpox to replicate and wreak havoc on the immune system.

The findings further our understanding of how the pox family of viruses work to subvert the immune system, the researchers say. They also believe their work could one day be used to develop new drugs to combat a variety of inflammatory and immunological disorders, including rheumatoid arthritis and some forms of heart disease.

The paper* describes the structure and actions of a powerful substance called interferon-gamma binding protein, which is notorious for the role it plays in helping the poxviruses to replicate. The research explores the interferon-gamma binding protein found in the mousepox virus -- one of the family of viruses that also includes smallpox, monkeypox and cowpox.

"Cracking open and describing the structure and actions of interferon-gamma binding protein is incredibly exciting, given the important role this substance plays in subverting the immune system," said Mark Buller, Ph.D., professor of microbiology and immunology at the Saint Louis University School of Medicine and one of the study's authors. "This breakthrough is something that many others have tried and failed to achieve."

Normally when a virus enters the bloodstream, the immune system responds by producing a substance called interferon-gamma, which assists the development of the immune response that's responsible for ridding the body of the virus.

Poxviruses, however, all come encoded with a potent weapon to evade the immune system: interferon-gamma binding protein. As its name implies, the protein literally binds to interferon-gamma and immobilizes it, preventing it from marshalling the immune system's defenses. The poxvirus is then able to replicate and cause immense damage.

The research describes how interferon-gamma binding protein looks and behaves on the molecular level during this process, something not previously understood.

"The poxviruses are able to evade the immune system very skillfully," Buller said, "so we wanted to identify exactly how these viruses work -- what makes them so effective and efficient."

Buller added that the findings have great potential for use in developing drugs that target immunological and inflammatory disorders, including a type of heart disease called atherosclerosis (sometimes referred to as hardening of the arteries), inflammatory bowel diseases (such as Crohn's disease and ulcerative colitis) and rheumatoid arthritis.

Of all the poxviruses, smallpox in particular has played a gruesome role in human history. The virus is estimated to have caused between 300 million and 500 million deaths in the 20th century alone. Though smallpox was declared officially eradicated in 1979, many experts fear that clandestine samples of the virus may have survived -- thus making it a major bioterrorism concern.

"The damage that the smallpox virus has done to mankind is horrific and enormous, which is why we think it's so important to understand more about the poxviruses and how they operate," Buller said. "The more knowledge we have, the better we should be able to cope with other major viruses and diseases in the future."

Buller pointed to co-author Tony Nuara as being critical to the team's success in understanding more about interferon-gamma binding protein. Nuara, now a fourth-year student at Saint Louis University School of Medicine, was working on his Ph.D. in molecular microbiology when taking part in the research effort.

"Without Tony, this research wouldn't have happened," Buller said. "He solved huge numbers of problems and figured out some answers to puzzling questions that previously had no answer."

Mark R. Walter, Ph.D., associate professor of microbiology at the University of Alabama at Birmingham and the paper's senior author, also noted the efforts of co-authors Sung Il Yoon, Ph.D., Brandi C. Jones, Naomi J. Logsdon and Leigh J. Walter, all of whose work contributed to determining the three-dimensional structure of the binding protein.

"The structure provides a visual blueprint to guide our future studies on interferon-gamma binding protein, which one day may be used to prevent inflammatory disease," Mark Walter said. "This is clearly a notable achievement."

*The research has been published in an early online edition of the Proceedings of the National Academy of Sciences. Jill M. Schriewer of Saint Louis University was also a co-author of the study.

The research was funded by grants from the National Institutes of Health, the UAB Center for Emerging Infections and Emergency Preparedness, and the American Heart Association.

Adapted from materials provided by Saint Louis University, via EurekAlert!, a service of AAAS.

Read the rest of this entry »

Malaria Vaccine Trials Begin Using 'Chimpanzee Virus'

Daily Science Journal (Feb. 1, 2008) — Trials are underway for a new vaccine to combat the most deadly form of malaria. For the first time ever, researchers will use a virus found in chimpanzees to boost the efficacy of the vaccine.

Malaria, caused by Plasmodium parasites, is one of the world's deadliest killers, killing over a million people each year, mainly women and young children in Africa and SE Asia. The most deadly species , P. falciparum, is responsible for 80% of malaria infections and 90% of deaths. As yet, there is no vaccine against malaria. This is because, for much of their life-cycle, the parasites responsible for infection live inside cells, where they cannot be reached by antibodies.

The trials will take place at the University of Oxford's Jenner Institute, led by its Director, Professor Adrian Hill.

"We urgently need a vaccine to help in the fight against this deadly killer," says Professor Hill, a Wellcome Trust* Principal Research Fellow. "Malaria parasites are able to outwit our immune system by hiding out in the body's cells, however. Finding a way to generate enough immune cells and antibodies to identify and destroy the parasites will be the key to preventing infection."

The vaccine being developed and trialled by Professor Hill's team in collaboration with Okairòs uses the company's genetically-modified chimpanzee adenovirus to produce the malaria antigen and to stimulate a response to the vaccine in the body. Adenoviruses appear to be particularly potent for increasing the immune response to the malaria vaccine. However, because human adenoviruses, which cause diseases including the common cold and gastroenteritis, are widespread, most people have developed some immunity towards them. Using a chimpanzee adenovirus ensures that a recipient is unlikely to have resistance to this component of the vaccine.

"Chimpanzees have their own set of adenoviruses which rarely infect humans, so we have not built up immunity to them," explains virologist Dr Sarah Gilbert at the Jenner Institute. "This is why we have chosen such a virus to form the backbone of the new vaccine."

Professor Hill's team is currently recruiting for more volunteers for the first trials, which are to assess the safety of the vaccine. Because the active component of the adenovirus is removed, however, there is no danger of transmission to the human of the original chimpanzee virus.

The trial will also be measuring the response of the immune system. The team hopes to generate a response from CD8+ T-cells (sometimes known as killer cells) that should kill the parasites when they enter the liver, where they multiply undetected. However, if the T-cells do not kill all of the parasites, any that escape from liver into the bloodstream will still be able to enter red blood cells and cause illness.

The group plans to test a second vaccine which would then target the parasites in the bloodstream and red blood cells.

"Our ultimate goal is a combination product which targets the parasite at both the liver stage and the blood stage," says Professor Hill. "Few people still think that you can get really strong protection from malaria based on a single component."

Over a dozen vaccines have now been made by scientists at the University of Oxford and taken into clinical trials, but this is the first vaccine to have also been manufactured within a UK university, according to Professor Hill.

*Funding was provided by the Wellcome Trust.

Adapted from materials provided by Wellcome Trust, via EurekAlert!, a service of AAAS.

Read the rest of this entry »

New Skin-healing Chemicals, Green Tea And The 'Asian Paradox'

Daily Science Journal (Aug. 30, 2007) — Researchers have made synthetic lipids called pseudoceramides that are involved in skin cell growth and could be used in treating skin diseases in which skin cells grow abnormally.

Ceramides are lipids found in the outermost skin layer called the stratum corneum, which is made of dead skin cells and mainly serves as a physical barrier. Ceramides' main biological function is to control how skin cells grow and differentiate -- a process through which skin cells become specialized.

Scientists have created in the laboratory synthetic ceramides, called pseudoceramides, to treat skin diseases such as atopic dermatitis, a form of eczema characterized by red, flaky and very itchy skin; psoriasis, a disease that causes red scaly patches on the skin; and glucocorticoid-induced epidermal atrophy, in which the skin shrinks due to skin cell loss.

Jeung-Hoon Lee and colleagues have developed a new series of pseudoceramides and examined their effects on skin cells. They found that three pseudoceramides called K6PC-4, K6PC-5, and K6PC-9 significantly increased the amount of proteins produced when skin cells differentiate. These results were obtained both on cultured skin cells and on a reconstituted epidermis. K6PC-4, K6PC-5, and K6PC-9 may be used to treat skin diseases arising from abnormal growth of skin cells, the scientists concluded.

Article: "Novel synthetic ceramide derivatives increase intracellular calcium levels and promote epidermal keratinocyte differentiation," by Yoo Bin Kwon, Chang Deok Kim, Jong-Kyung Youm, Hyung Sub Gwak, Byeong Deog Park, Seung Hun Lee, Saewha Jeon, Bo Joong Kim, Young-Joon Seo, Jang-Kyu Park, and Jeung-Hoon Lee

Adapted from materials provided by American Society for Biochemistry and Molecular Biology, via EurekAlert!, a service of AAAS.

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

Add On Article :

Green Tea And The 'Asian Paradox'

There is a lower incidence of cardiovascular disease and cancer in Asia where people smoke heavily, which may be accounted for by high consumption of tea, particularly green tea, according to a review article published by a Yale School of Medicine researcher.

"We do not yet have a full explanation for the 'Asian paradox,' which refers to the very low incidence of both heart disease and cancer in Asia, even though consumption of cigarettes is greater than in most other countries," said Bauer Sumpio, M.D., professor and Chief of Vascular Surgery in the Department of Surgery. "But we now have some theories."

Sumpio, the lead author of the review in the Journal of the American College of Surgeons, said he and his colleagues reviewed more than 100 experimental and clinical studies about green tea in writing the article.

He said one theory is that the average 1.2 liters of green tea consumed daily by many people in Asia offers the anti-oxidant protective effects of the polyphenolic EGCG. EGCG may prevent LDL oxidation, which has been shown to play a key role in the pathophysiology of arteriosclerosis. EGCG also reduces the amount of platelet aggregation, regulates lipids, and promotes proliferation and migration of smooth muscle cells, which are all factors in reducing cardiovascular disease, he said.

Sumpio said other reports show that EGCG prevents growth of certain tumors. Tea, according to studies, also can improve gastrointestinal function, alcohol metabolism, kidney, liver and pancreatic function, protect skin and eyes and alleviate arthritis. Tea has been used in managing and preventing allergies, diabetes, bacterial and viral infections, cavities, reduce or cure diseases with an inflammatory component and improve neurologic and psychological health.

"More studies are necessary to fully elucidate and better understand green tea's method of action, particularly at the cellular level," Sumpio said. "The evidence is strong that green tea consumption is a useful dietary habit to lower the risk for, as well as treat, a number of chronic diseases. Certainly, however, smoking cessation is the best way to prevent cardiovascular disease and cancer."

Reference: Journal of the American College of Surgeons 202: 813-825 (May 2006)

Adapted from materials provided by Yale University.

Read the rest of this entry »

Researchers Explain Carbon Monoxide's Anti-inflammatory Effects

Daily Science Journal (Jul. 1, 2007) — In a study appearing in the April 2007 issue of The FASEB Journal, scientists from Harvard University and the University of Pittsburgh have shown for the first time that the anti-inflammatory effects of carbon monoxide originate within cells' own molecular engines, mitochondria.

Specifically, mitochondria react to low levels of carbon monoxide by releasing chemical signals that reduce or shut down the body's inflammatory response, raising the possibility for the development of new anti-inflammatory therapies, one of which may be low levels of inhaled carbon monoxide.

According to the study's first author, Brian S. Zuckerbraun, M.D. of the University of Pittsburgh, "this study may contribute to our understanding and development of controlled carbon monoxide as a therapeutic agent."

Inflammation is a normal defense mechanism used by the body to ward off infection, but over time, severe or chronic inflammation can damage tissues. In some cases, such as in organ transplantation, the body's inflammatory response over the short-term also can cause more harm than good. Current approaches to controlling inflammation are not always successful, making the need for new approaches urgent. In particular, inhaled medical grade carbon monoxide has been shown to be useful in animal models for organ transplantation, vascular injury, inflammatory bowel disease, organ injury resulting from severe blood loss, as well as experimental hepatitis and experimental pulmonary hypertension.

"The findings described in this study are particularly relevant, given that April is National Donate Life Month," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Transplants are rejected because of inflammation gone awry. If we block inflammation, as with carbon monoxide or agents that release it in a controlled fashion, we can not only make transplantation safer, but extend its benefits to many more who need it."

Adapted from materials provided by Federation of American Societies for Experimental Biology, via EurekAlert!, a service of AAAS.

Read the rest of this entry »