A new study shows how rhesus monkeys with a low social rank have an altered immune response. Investigating 9,000 genes, the team demonstrates the implications for the immune system of being at the bottom of the ladder.

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Research in monkeys has shown social rank may affect the immune system.

In America, people in the lowest socioeconomic bracket are more prone to heart disease and diabetes.

The difference in life expectancy between those at the lower end of the social ladder and those at the top differ by more than a decade.

In fact, the difference between the life expectancy of the richest 1 percent and the poorest 1 percent is estimated to be 14.6 years.

There are, of course, a number of factors at work, including disparity in access to medical care and differences in habits such as exercise, diet, and smoking.

However, it is becoming ever clearer that the chronic stress of life at the bottom can negatively influence the way in which the immune system functions.

A team of researchers from a number of institutions, including Duke University, NC, set out to measure these immune differences in rhesus monkeys at the Yerkes National Primate Research Center of Emory University, GA.

Self-organizing rhesus social groups

In the first leg of their research, the team introduced 45 unrelated female monkeys that had never met. They brought them to meet each other one at a time and observed how they interacted - which individuals bullied and which cowered.

The group automatically organized themselves into a social hierarchy with the individuals who had first arrived taking the top spots and those arriving last fitting into the bottom rungs.

Once the pecking order was established, the investigators extracted immune cells from the monkeys and measured the activity of around 9,000 genes.

Of these genes, more than 1,600 were expressed differently in lower- and higher-ranking females. The differences were particularly prevalent in natural killer cells - a type of white blood cell considered the first line of defense against infection.

As co-first author Noah Snyder-Mackler says, "Social adversity gets under the skin."

The next question to answer was whether or not the changes in natural killer cells could be rectified or altered. To investigate this, they split the female monkeys into nine new social groups.

Can the immune changes be reset?

As before, the females automatically sorted themselves into ranks, based on who had arrived first. This resorting of ranks meant that some of the previously low-ranking females were now in the upper echelons and vice versa.

When the blood of the recently elevated rhesus monkeys was tested, the researchers found that the pattern of which genes were turned on and off was more similar to the high-ranking females. In other words, the immune deficits were not set in stone and were open to manipulation by shifts in hierarchy.

Co-author Jenny Tung, assistant professor of evolutionary anthropology and biology at Duke University, says: "This suggests the health effects of status aren't permanent, at least in adulthood."

These findings provide backing for the theory that it is not just a high socioeconomic standing that promotes good health, but also that a low status can actively produce negative health outcomes.

Interestingly, the differences between higher- and lower-ranking females' immune systems were even more pronounced when they faced a potential pathogen. When a bacterial toxin - lipopolysaccharide - was introduced to their white blood cells, pro-inflammatory genes from subordinate females were observed entering an accelerated mode.

This over-eagerness to respond to a threat may help explain why inflammatory conditions are more common in lower socioeconomic strata of society. Although an inflammatory response can save the life of an organism, if the response is triggered too often, or for long periods of time without cause, it can be detrimental to health.

If these findings ring true for humans, too, it could help design interventions in which earlier treatments are given to those who may be at highest risk; it could also help prevent methods of controlling inflammatory-based illnesses in certain groups of American society.

Learn how the immune system might influence our social behavior.