Photo of a woman feeling bad
Scientists say the immune mechanism used to fight illness can also take its toll on the body

Why we feel worse when our bodies are trying to get better

22 March, 2012

Natural Health News — A new analysis has tried to explain why we sometimes feel worse when our immune system is trying to make us well.

Two US researchers have offered a new perspective on a component of the immune system known as the ‘acute-phase response’, a series of systemic changes in metabolic function, physiology and blood protein levels that sometimes occurs when infection takes hold.

This normal response to invasion by bacteria, viruses or other pathogens, puts healthy cells and tissue under serious stress, and is actually the cause of many of the symptoms we associate with being sick.

A healing crisis

Practitioners of alternative medicine sometimes call this experience a ‘healing crisis’.

The question is why would the body evolve to produce symptoms of sickness when it is actively involved in healing?

The authors of this new analysis believe the answer becomes clear when we view the acute-phase response and its symptoms in terms of what they have dubbed “immune brinksmanship.”

Immune brinksmanship according says co-author Edmund LeGrand of the University of Tennessee, Knoxville, is a gamble the body takes that its immune responses will harm the invading pathogen morethan itself.

A biological ‘trade dispute’

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 says.

The acute-phase response creates stress in several ways. It raises body temperature and causes loss of appetite and mild anaemia. 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. For example, why reduce food intake just when one would expect more energy would be needed to mount a strong immune response?

Likewise, 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 and co-author Joe Alcock (University of New Mexico) offer some answers.

The body has the upper hand

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 pummelling 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 says.

An intelligent risk

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, say the authors, systemic stressors when properly regulated do more preferential harm to invaders, which may be why not only humans, but other mammals, reptiles, fish, and even invertebrates experience a similar response to healing.

The article appears in the Quarterly Review of Biology.