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Early exposure. The Shuar people of the Amazon do not suffer from a chronic inflammatory response.

Courtesy of the Shuar Health and Life History Project

'Silent Killer' May Be Disease of the Affluent

From an early age, the indigenous Shuar people of the Ecuadorian Amazon are exposed to an army of parasites, viruses, and other microbes. But if children survive to adulthood—no guarantee, given that they're three times more likely to die before the age of 5 than children in the United States and Canada—they seem to end up with more efficient immune systems than people living in industrialized nations. That's the conclusion of a new study, which adds weight to the idea that early exposure to pathogens confers long-term health benefits.

Inflammation is part of a healthy immune response, allowing the body to orchestrate an onslaught of immune cells and chemicals to heal an injury and fight infection. But sometimes the process goes awry, as when obesity, periodontal disease, stress, or a chronic infection such as herpes continuously stimulates the immune system, causing chronic, low-grade inflammation. This can eventually interfere with the body's healthy tissues, increasing the risk of heart attacks, stroke, diabetes, cancer, and autoimmune disease. In the West, chronic inflammation is known as a "silent killer."

Chronic inflammation is widespread in industrialized nations, and researchers have wondered if it's also rampant in nonindustrialized nations, where fewer people are overweight, for example, but where more people are exposed to acute infectious disease.

To find out, biological anthropologists Thomas McDade of Northwestern University in Chicago, Illinois; Josh Snodgrass of the University of Oregon in Eugene; and colleagues measured the levels of C-reactive protein (CRP) in the blood, a marker of a person's inflammatory response. The researchers collected blood samples 4 weeks in a row from 52 adults between the ages of 18 and 49 in Shuar communities near the town of Sucúa in the lowlands of the Amazon in Ecuador. They found that some of the adults had a high level of CRP at a single point in time, indicating an acute inflammatory response to an infection. But not a single Shuar tested above 3 milligrams per liter-the benchmark for a chronic inflammatory response in the United States. This differs from the pattern in industrialized nations, where CRP is chronically elevated in about one-third of adults, the team reports online this week in the American Journal of Human Biology.

In the Shuar, says McDade, "CRP goes up when you need it, but it is almost undetectable when you don't, after the infection resolves." And that suggests that exposure to microbes early in life may fine-tune the immune system so that it can regulate its response to acute and low-grade infections more efficiently—much in the same manner as the so-called "hygiene hypothesis" predicts that children who are exposed to microbes, such as on farms, for example, are less likely to develop allergies later in life. Indeed, the rural Shuar foragers are very lean and healthy, with low rates of cardiovascular disease and diabetes, says Snodgrass.

Others agree with these conclusions. "McDade's general point that the immune system is dysregulated in the absence of pathogen exposure early in life is extremely important—and seems to have downstream consequences on many seemingly unrelated diseases," says biological anthropologist Michael Gurven of the University of California, Santa Barbara.

In the absence of these organisms that co-evolved with us, people living in industrialized nations developed a defect in their immune regulation, says microbiologist Graham Rook of University College London, who proposed in 2003 that with urbanization, humans are not exposed to as many pathogens, such as parasites and bacteria in dirty water and mud. Poorly controlled inflammation, he notes, "occurs not in people living in third-world countries, riddled with infections, but rather in rich, infection-free, urbanized populations." In other words, says McDade, "chronic inflammation may be a disease of affluence."