Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Defective immune system response to smallpox vaccine detailed in new study

22.03.2006


People with Eczema may benefit from finding



Scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), have identified a defect in the immune response of people with the skin condition atopic dermatitis that puts them at risk of developing serious complications following smallpox vaccination. Led by Donald Y.M. Leung, M.D., Ph.D., of the National Jewish Medical and Research Center in Denver, the researchers used laboratory-grown human skin cells to show that an immune system protein called LL-37 is critical in controlling replication of vaccinia virus, the live virus that is the key component in standard smallpox vaccine.

The investigators are part of NIAID’s Atopic Dermatitis and Vaccinia Network, which was created in 2004 to integrate clinical and animal research aimed at reducing the risk of eczema vaccinatum, a potentially deadly complication of smallpox vaccination. Eczema vaccinatum occurs almost exclusively in people who have a history of atopic dermatitis, a common, non-contagious skin disorder also known as eczema.


"This new research, the first to be published by Atopic Dermatitis and Vaccinia Network scientists, illuminates one potential mechanism leading to eczema vaccinatum and improves our understanding of the immune responses to smallpox vaccine of people with atopic dermatitis," says NIAID Director Anthony S. Fauci, M.D.

Published in this month’s issue of Immunity, the study details how the overproduction in skin cells of inflammation-promoting molecules called interleukin-4 and interleukin-13 (IL-4 and IL-13) hampers LL-37 activity in people with atopic dermatitis. LL-37, a small protein produced in skin cells, is part of the body’s first line of defense against invaders. Earlier research by Dr. Leung and his colleagues suggested that LL-37 is critical in controlling the spread of vaccinia virus.

In the current study, the investigators used skin samples taken from people with atopic dermatitis (as well as samples taken from healthy volunteers without skin disease and from people with another skin condition called psoriasis) to further investigate how dysfunctions in the immune response of people with eczema set the stage for eczema vaccinatum. When exposed to vaccinia virus, the skin samples from healthy volunteers and from those with psoriasis reacted by producing more LL-37. As a result, the replication of the virus was controlled and eventually halted. In contrast, LL-37 production was minimal in skin samples from people with atopic dermatitis and vaccinia replication was poorly controlled. Next, the scientists exposed skin samples from people with atopic dermatitis to vaccinia, and then added LL-37. With the LL-37 supplement, the skin cells successfully controlled the viral replication.

Dr. Leung and his group then looked more closely at why vaccinia infection fails to induce LL-37 production in atopic dermatitis skin. Comparing immune responses of skin cells grown in the lab from healthy volunteers and from people with atopic dermatitis, the researchers found that the latter skin samples produced excessive amounts of IL-4 and IL-13. Adding IL-4 and IL-13 to skin cells from healthy volunteers prior to vaccinia exposure reduced levels of LL-37 production. Conversely, when the scientists applied IL-4- and IL-13-neutralizing antibodies to skin samples from people with atopic dermatitis, LL-37 production increased significantly.

Together, these findings suggest a rationale for new treatment approaches to eczema vaccinatum, notes Dr. Leung. One approach involves developing drugs to mimic the action of LL-37 or developing LL-37-containing creams that could be applied to the skin in order to boost its ability to contain vaccinia virus infection. Another approach could be to develop agents to neutralize IL-4 and IL-13. Although no such drugs are currently marketed, compounds that can neutralize IL-4 and IL-13 are under study as possible asthma and allergy treatments, Dr. Leung says, and might also be applied to eczema vaccinatum treatment.

Smallpox vaccine, which is made with live vaccinia virus (a close relative of the virus that causes smallpox), has not been routinely given in the United States since the early 1970s. But recent concerns about the possibility of a bioterrorist attack using smallpox virus prompted authorities to reinstate voluntary smallpox vaccination for specific groups, such as military personnel. In the first five months of 2003, the U.S. Department of Defense vaccinated more than 450,000 personnel against smallpox. During this period, the majority of those who deferred vaccination cited atopic dermatitis or other skin conditions as the main reason.

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

More articles from Studies and Analyses:

nachricht Study relating to materials testing Detecting damages in non-magnetic steel through magnetism
23.07.2018 | Technische Universität Kaiserslautern

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

'Building up' stretchable electronics to be as multipurpose as your smartphone

14.08.2018 | Information Technology

During HIV infection, antibody can block B cells from fighting pathogens

14.08.2018 | Life Sciences

First study on physical properties of giant cancer cells may inform new treatments

14.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>