HCV New Drugs

Interferon's used during hepatitis C standard therapy or newer triple therapy works by stimulating the body's immune response, often leading to side effects including flu-like symptoms, fever, and muscle aches.

Interferon was discovered in 1957 by Alick Isaacs and Jean Lindenmann, it wasn't until 1996 that the FDA approved alfa interferon for the treatment of hepatitis C. In a recent article published online last month by the journal PNAS researchers presented the first clinical assessment of how interferon works and fights HIV and Hepatitis infections, view the USCF article here.

The Immune System
When I was undergoing standard hepatitis C therapy I asked my physician why I ran a low-grade fever. He explained in simple terms, it went something like this - "Interferons (IFNS) are made naturally in the body as a response to the presence of viruses and "interfere" with viral replication, hence their name. The symptoms experienced during a fever are related to the production of IFNs during infection.  Because you're injecting the drug interferon you may experience the same symptoms. 

Interferon-Fever 
On a high note researchers presented a study last year at the 2011 AASLD meeting, which found people who experience a fever soon after starting interferon-based therapy are more likely to experience early virological response, view the abstract here.

This brings us to an article today in the news highlighting the immune system. When the immune system jumps start the host may feel the ill effects. This article answers the question - "Why the immune system often makes us worse while trying to make us well." 

Why getting healthy can seem worse than getting sick

A new article in The Quarterly Review of Biology helps explain why the immune system often makes us worse while trying to make us well.

The research offers a new perspective on a component of the immune system known as the acute-phase response, a series of systemic changes in blood protein levels, metabolic function, and physiology that sometimes occurs when bacteria, viruses, or other pathogens invade the body. This response puts healthy cells and tissue under serious stress, and is actually the cause of many of the symptoms we associate with being sick.

"The question is why would these harmful components evolve," asks Edmund LeGrand (University of Tennessee, Knoxville), who wrote the paper titled with Joe Alcock (University of New Mexico). The researchers contend that answer becomes clear when we view the acute-phase response in terms of what they call "immune brinksmanship."

The immune brinksmanship model "is the gamble that systemic stressors will harm the pathogens relatively more than the host," LeGrand said. The concept, he explains, is akin to what happens in international trade disputes. When one country places trade sanctions on another, both countries' economies take a hit, but the sanctioning country is betting that its opponent will be hurt more.
"One of our contributions here is to pull together the reasons why pathogens suffer more from systemic stress," LeGrand said.

The acute-phase response creates stress in several ways. It raises body temperature and causes loss of appetite and mild anemia. At the same time, certain vital nutrients like iron, zinc, and manganese are partially sequestered away from the bloodstream.

 Some of these components are quite puzzling. Why reduce food intake just when one would expect more energy would be needed to mount a strong immune response? Zinc is essential for healthy immune function. Why pull it out of the bloodstream when the immune system is active? The benefits of a stressor like fever are fairly well known; heat has been shown to inhibit bacterial growth and cause infected cells to self-destruct. But what hasn't been clear is why pathogens should be more susceptible to this stress than the host.

LeGrand and Alcock offer some answers. For an infection to spread, pathogens need to multiply, whereas host cells can defer replication. Replication makes DNA and newly forming proteins much more susceptible to damage. It also requires energy and nutrients—which helps explain the benefits of restricting food and sequestering nutrients.

The act of invading a body also requires bacteria to alter their metabolism, which can make them more vulnerable to all kinds of stress, including heat.
Another reason pathogens are more vulnerable to stress is that the immune system is already pummeling them with white blood cells and related stressors at the site of the infection. That means that pathogens are already under local stress when systemic stressors are piled on. "In many ways, the acute-phase response reinforces the stress inflicted on pathogens locally at the infection site," LeGrand said.

As the term "brinksmanship" implies, there's an inherent risk in a strategy that involves harming oneself to hurt the enemy within. This self-harm leaves the body more vulnerable to other dangers, including other infections. Additionally, it is possible for the immune stressors to do more damage than required to control the pathogens.

"But in general, systemic stressors when properly regulated do preferential harm to invaders," LeGrand said. Viewed this way, it's not surprising that natural selection has utilized the stressful parts of the acute-phase response in mammals, reptiles, fish, and even invertebrates.
Edmund LeGrand and Joe Alcock, "Turning Up The Heat: Immune Brinksmanship In The Acute-phase Response." The Quarterly Review of Biology 87:1 (March 2012).
The premier review journal in biology since 1926, The Quarterly Review of Biology publishes articles in all areas of biology but with a traditional emphasis on evolution, ecology, and organismal biology. QRB papers do not merely summarize a topic, but offer important new ideas, concepts, and syntheses. They often shape the course of future research within a field. In addition, the book review section of the QRB is the most comprehensive in biology.
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