Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Experimental immune-boosting drug worsens TB in mice

13.04.2010
An experimental drug that boosts production of the immune system protein interferon worsens tuberculosis (TB) in mice, according to scientists from the National Institutes of Health.

The drug acts indirectly by drawing certain immune cells, in which Mycobacterium tuberculosis (M.tb) bacteria thrive, to the lungs. The findings may have potential implications for the care of people infected with TB, the authors note. The research is reported in the May 3 issue of Journal of Clinical Investigation, now available online.

"Although our research was conducted in mice, our combined findings suggest that reactivation of TB should be considered as a potential side effect if compounds that boost type I interferon production, like the one used in this study, are tested in people who may be infected with M.tb," says Alan Sher, Ph.D., of the National Institute of Allergy and Infectious Diseases (NIAID), NIH, who led the team of scientists.

Most people infected with M.tb do not develop active TB. Instead, the infection remains dormant, often for decades. Eventually, about 10 percent of people with latent infection do go on to develop active disease. Common triggers for reactivation include aging or other conditions that lower immunity.

Dr. Sher and his colleagues studied the effects of an experimental drug called poly-ICLC on immune responses to TB infection. Poly-ICLC stimulates the body to produce a potent immune system protein called type I interferon (type I IFN). Interferon was named for its ability to interfere with viral infections. Synthetic IFN is used to treat hepatitis B and C virus infections, as well as certain kinds of cancers.

In mouse studies, poly-ICLC protected the animals from viruses that can cause lethal infections, including pandemic influenza and SARS. It has also been shown to enhance the effects of several experimental vaccines when tested in animals. Poly-ICLC also is being tested in multiple human clinical trials as a possible cancer treatment when combined with cancer vaccines.

Earlier research into the effects of type I IFN on bacterial infections produced mixed results, notes Dr. Sher. Some studies showed that giving IFN to mice with non-tuberculous mycobacterial infections (Mycobacterium avium) lowered the amount of bacteria in their bodies. But in other studies, naturally occurring IFN appeared to promote rather than limit the growth of bacteria in mice infected with M.tb.

To sort out the mixed findings, NIAID investigator Lis R.V. Antonelli, Ph.D., dropped poly-ICLC into the noses of mice that had been infected with M.tb. The mice were infected either one day earlier to mimic an acute TB infection, or four months earlier to simulate a chronic TB infection. They were then compared with TB-infected, untreated mice. All the mice treated with poly-ICLC developed severe lung tissue damage. Moreover, levels of M.tb in their lungs were 100 times greater than in M.tb-infected mice that did not receive poly-ICLC.

Next, Dr. Antonelli performed a series of experiments to determine what kind of immune system cell was involved in hastening the disease in poly-ICLC-treated mice. Again, they compared poly-ICLC treated and untreated, M.tb-infected mice. In the treated group, the scientists found a fourfold increase in a specific subpopulation of immune cells called macrophages. In most infectious diseases, macrophages are drawn to the site of infection and help defend the host against disease. But when type I IFN production was elevated by poly-ICLC treatment, the surge in macrophages to the M.tb-infected lung actually harmed the host, notes Dr. Sher. TB bacteria live inside macrophages, and the specific subset detected in these experiments appears especially hospitable to M.tb.

Dr. Sher and his colleagues are currently testing the relevance of these findings to humans by determining whether under certain conditions type I IFN promotes the growth of M.tb in human macrophages. Such research could also provide important clues to exactly how and under what conditions latent TB is reactivated.

Dr. Antonelli, who was based at NIAID when the research was conducted, now works at Fiocruz, a government-sponsored research institute in Belo Horizonte, Brazil.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

The National Institutes of Health (NIH)—The Nation's Medical Research Agency—includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Reference: LRV Antonelli et al. Intranasal poly-IC treatment exacerbates tuberculosis in mice through the pulmonary recruitment of a pathogen-permissive monocyte/macrophage population. Journal of Clinical Investigation DOI: 10.1172/JCI40817 (2010).

Anne A. Oplinger | EurekAlert!
Further information:
http://www.niaid.nih.gov

More articles from Life Sciences:

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>