Life for female rhesus macaques is a little like being trapped in high school—groups have intense social hierarchies where those at the top spend more time socializing and those at the bottom endure passive-aggressive overtures from peers. A study published today in Science reveals that social status in macaques can actually impact their immune system, resulting in significant differences in immune function between high- and low-status monkeys.

In the study, which was a collaboration among scientists at Duke University, Emory University and the University of Montreal, researchers organized 45 adult female macaques into social hierarchies and measured the animals’ immune functions. They found that high-status monkeys have more immune cells needed to combat viral attacks, whereas low-status monkeys have heightened activity in cells that respond to bacterial invaders. Moreover, when the researchers artificially manipulated the monkeys’ social ranks, their immune functions changed accordingly. The findings suggest a causal relationship between social rank and immune function that is reversible based on changing social conditions.

For decades scientists have known that for humans and other social animals, social interaction can be a strong predictor of health and disease. In fact, a recent longitudinal study found that American men of the highest socioeconomic status live almost 15 years longer than men of the lowest socioeconomic status, and similarly high-status women live about 10 years longer. However, scientists have struggled to unravel the causes of these dramatic differences. Do people of lower socioeconomic status start out sicker? Do they engage in more risky behaviors, such as smoking? Do they lack access to good health care? Or does social status cause physiological changes that adversely affect health over time?

To study the relationship between social status and health in a more controlled setting, the researchers looked at immune function in macaques, a highly social primate species. Female macaques form linear, hierarchical groups, where higher-status monkeys spend more time grooming (a behavior that cements social bonds), whereas low-status monkeys are excluded from grooming, and experience more harassment and social isolation. In the wild, a macaque will enter the hierarchy right below her mother, but in captivity, the most recent addition to a group tends to have the lowest status. “That gives us the chance to take individuals that don't know each other, randomize where they end up in a status hierarchy, and then basically watch what happens,” explains study co-author Jenny Tung of Duke.

In the first part of the study, Tung and her colleagues organized 45 female macaques into nine equally sized social groups and observed them for a year. When they analyzed blood samples from the monkeys, they found that, compared with their low-status counterparts, the high-status animals had greater expression of genes that produce natural killer cells, which are responsible for containing viral infections. By contrast, blood samples from the low-status monkeys mounted a much stronger inflammatory response when confronted with a compound that mimics a bacterial attack. Overall, thousands of genes were expressed differently between high- and low-status monkeys.

To investigate whether the difference in immune response was truly caused by social status, the researchers then reshuffled the macaques into new social groups—all the top-ranking monkeys were grouped together, as were the second-ranking monkeys, the third-ranking monkeys, and so on. Tung compares it to creating a group composed entirely of CEOs: “Some CEOs would get to remain CEOs, but some would go all the way down to the bottom.”

They found strong evidence that social status alone can cause immune changes: immune response in the macaques changed to match their new social rank. “There's really a lot of plasticity in the way the cells are responding to infection that is directly controlled by social status,” says study co-author Luis Barreiro of McGill University. Tung adds that “If you can change your social condition, your immune gene expression is going to look a lot more like where you are now, instead of where you used to be in the past.”

But what do these immune responses tell us about macaque health? According to Tung, all of the monkeys had an inflammatory response, which is needed to battle bacterial infections. However, the heightened response in the low-status monkeys could lead to tissue damage, as the immune system turns on the body’s own cells. Tung hypothesizes that long-term, such inflammation may cause health issues. “Some of the diseases that we know about that show the strongest social gradients in health in humans are in fact diseases that are closely associated with inflammation,” she says.  

Frans de Waal, a primatologist at Emory University who was not involved in the study, praises it for convincingly establishing a causal relationship between social status and immune response in macaques, a step he describes as “very powerful and very much needed” in the field.   

Robert Sapolsky, a neuroendocrinologist at Stanford University who studies primates but was not involved in the study, wrote a perspective on the research also published today in Science. “We know that the most pounding, permeating form of social subordination in humans—poverty—produces poor health through a variety of mechanisms,” he wrote in an email. “The study adds an important additional pathway by which this might occur.”

For Tung, however, the outlook is not entirely bleak. “We've convincingly shown that chronic social stress by itself can change the way our body works,” she says, “But the hopeful message is how responsive [immune] systems are to changes in the social environment. That's really different than the possibility that your social history stays with you your entire life.”