May 2011 Edition

Inflammation: At the Heart of Health Epidemics

The prosperity and invention of the 20th century made life easier. Machines replaced manual labor, and manufacturing churned out margarine, oils, ice cream and sugared drinks. But the technological advances that reduced physical demands and increased universal access to diets rich in fat and sweets have also produced some unpleasant side effects: obesity, diabetes, heart disease and possibly even cancer. Those diseases are at the heart of America’s biggest health epidemics, and until relatively recently physicians have treated them separately. However, although the disease processes differ, it is becoming increasingly apparent that a single aspect of their underlying pathology is shared: inflammation.

 

“Acute inflammation at the site of an acute injury keeps us alive, it keeps us from dying of an acute infection. Chronic inflammation is when the same system that is there for acute inflammation starts to, if you will, attack ourselves. It finds a site of injury inside of ourselves and starts trying to fix it,” Explains Penn.

 

But sometimes it never actually fixes the problem and so the system never shuts off. White blood cells furiously repairing an injury in an unregulated manner recruit more white blood cells and so on. The human immune system becomes an endless positive feedback loop that becomes dangerous—ultimately damaging tissue and leading to disease. Diabetes, Crohn’s disease, atherosclerosis, rheumatoid arthritis, Alzheimer ’s disease, asthma and cancer all have been demonstrated to have an inflammatory component.

“The point of evolution was for us to develop systems that we would survive until we could have babies and then our babies could go on. We didn't really evolve to minimize chronic inflammation. We evolved to maximize acute inflammation – and the system's rigged to be very good. The problem is if you now live 70 years and you have the wrong diet and you cause internal injuries if you will, chronic inflammation sets up and causes chronic disease,” says Penn.

 

One of the most heavily researched inflammatory-linked chronic diseases to-date is heart disease. More than three decades ago, Russell Ross proposed that atherosclerosis , or hardening of the arteries, was the result of the inflammatory response to an injury to the vessel walls^1,2. Ross argued that the artery becomes injured, that injury causes inflammation, and that when the inflammation doesn't go away a process is triggered that begins to lay down atherosclerotic plaques. Today it’s believed that that one initial injury may be the oxidation of lipids like HDL, which explains why high cholesterol can be an important risk factor in heart disease, but is far from the whole story.

Ross’s idea became the foundation for what we now know about how inflammation causes and/or participates in a variety of disease processes. But perhaps more importantly, it has led physicians and researchers to new ways of predicting and ultimately treating those diseases. In the case of heart disease, novel biomarkers that predict the stage in the inflammatory process can already give physicians crucial insight into how to better manage their patients explains Penn.

“So not only can we define which patients are at risk, but also define where on a risk spectrum they are. Are they early in the process-- and some day may be at risk to have disease? Do they have disease but it's not particularly active? Do they have disease and it in fact is active and they are at risk for an event? I think that's a great model for where we could go down the road for other chronic inflammatory diseases,” Penn says.

The growing understanding of inflammation has also given physicians a better understanding of how inflammatory diseases like arthritis, diabetes, and heart disease are linked. For example, people with rheumatoid arthritis are 5 times more likely to suffer a heart attack – regardless of their cholesterol levels- simply because they have higher levels of inflammation. And cholesterol lowering drugs like statins also have beneficial effects on arthritis, because they have powerful anti-inflammatory components.

What’s more, the advancements in inflammation science have begun to illuminate the ways in which diet and lifestyle changes can work with or against disease. The mechanism of the link between obesity and a variety of different diseases can now be explained by the discovery that fat cells actually secrete pro-inflammatory hormones. Losing weight reduces the hormones and quells the inflammation that helped fuel the disease. Depression, which has also been shown to raise levels of inflammation via the vagal nerve, likewise increases the risk for inflammatory-linked diseases. It’s not surprising then that treatments like biofeedback, meditation and yoga that are thought improve vagal nerve function can actually reduce that systemic inflammation and improve disease outcomes.

But Penn says it’s important to keep in mind that inflammation isn’t all bad. In fact some of it is necessary. Drugs like steroids that wipe out the immune system completely can have effects equally disastrous to an immune system out of control because the body isn’t able to heal. Patients who have been given steroids after a heart attack are much more likely to have their hearts rupture. The reason? Because necessary scar tissue was never allowed to form help the heart recover from damage. Inflammation is also required to send the SOS to the body’s own repair system - stem cells. Without the initial inflammatory signaling, they won’t come to an injury site and promote repair.

Although our understanding of inflammation and disease has come a long way in the last three decades, we’re really just at the beginning , and the tools for detecting and treating inflammation are arguably still crude. Medicine of the future, says Penn, won’t just block the immune system with a blanket approach. Instead, it will systematically target it and regulate it in a controlled and meaningful way – so that it can do the job it was meant to do: protect us from disease, not cause it.
 

References

1.  Ross R and Glomset JA.  The pathogenesis of atherosclerosis (first of two parts).  N Engl J Med. 1976; 295:  369-377.  Abstract

2.  Ross R and Glomset JA.  The pathogenesis of atherosclerosis (second of two parts).  N Engl J Med.  1976; 295: 420-425.  Abstract