A causal relationship between stress and the immune system has now been confirmed in humans, potentially offering insight into how chronic stress affects the body — particularly when associated with mental health conditions.

A paper published March 9 in Brain, Behavior, and Immunity reported that mild stress in humans leads to an increase in immune system activity, mainly blood monocyte levels. The researchers behind the work hope their results can clear the way toward understanding the larger impact that stress-related disorders can have on people.

"This study provides a stepping stone for future research investigating conditions associated with chronic stress and elevated levels of anxiety or depression, looking at the same readouts," Marcel van de Wouw, a postdoctoral researcher formerly at University College Cork in Ireland and the lead author of the study, told The Academic Times.

For example, the study says that, "A stress-induced increase in monocyte levels in humans could indicate that more monocytes are released from their reservoir than traffic into tissues."

Too many monocytes typically signals that there may be an underlying condition that the body is fighting, which requires many of these white blood cells. 

Either way, the findings express a concrete, direct relationship between continuous stress and the human immune system.

Immune systems and their blood monocyte levels, which induce inflammatory responses, are primarily activated when fighting infection. That takes up the attention of the immune system, making one more prone to developing other illnesses, too.

It's also known that the corticosteroid hormone released when a person is stressed can weaken the immune system. This makes one who is under lots of stress susceptible to other medical issues as well, similar to if they are fighting an infection. Another generally accepted phenomenon is that short- and long-term stress can lead to headaches, chest pain and stomach problems, among other things.

But the seriousness of all these associations is still murky due to the lack of research in humans, van de Wouw believes.

"Changes in monocytes have also been reported after chronic stress in mice. But once again, most work has been performed in mice," he said. "We thought that it would be important trying to translate these acute stress-related findings, observed in mice, to humans." 

Van de Wouw, who is now at the University of Calgary, hopes that his findings can address this gap in the literature. It is especially striking, according to the study, that the findings contradict some mice studies that indicated lower monocyte levels after an acute stressor.

The type of stress considered in the experiments, called acute stress, is triggered by minor stressors and is the usual manifestation that people experience. Such stressors can range from feeling restless waiting in a long line to receiving criticism or rushing to meet a deadline at work. 

Acute stress is also an extremely common side effect of mental health concerns such as depression, generalized anxiety disorder and obsessive-compulsive disorder. Being a side effect of an ongoing condition turns it into a pattern, and when it's a pattern, it's characterized as chronic stress.

Van de Wouw set out to find how acute and chronic stress affect the immune systems of healthy females. He explained that they tested females because of available blood samples from a previous study, not because they anticipated outcome variation based on sex of an individual.

"The stress-responses observed in this study provide insights into how a 'normal, healthy' immune system reacts to an acute stressor," he said, emphasizing that this study should be seen as a baseline for immune stress-response.

The increase in immune system monocyte levels was examined by comparing the count in healthy females before and after they experienced an acute stress event. The "event" that the team used is called the socially evaluated cold pressor test. 

"The acute stressor used in this study … has been used in many other studies, allowing us to more easily compare our results with other studies from our — and other — labs," van de Wouw said.

It's a standardized technique used to measure stress-related variables that involves immersing a subject's hand into ice water and telling them that they will be both monitored and videotaped while it happens, with the former addressing the physical aspect of stress and the latter the psychological aspect. When the researchers checked the monocyte levels after submersion, they saw an increase.

The study noted that other immune system receptors also trended toward increased levels, independent of the blood monocyte count. 

"We can't really say yet whether a bigger impact of acute stress on these monocyte parameters is good or bad per se," van de Wouw said. He urged further testing before coming to any conclusory statements beyond the causal relationship. 

"When we understand how these specific immune parameters change in such individuals [with mental health conditions] compared to healthy individuals," he said, "then we will be a lot closer to being able to say which types and degrees of stress-induced immune responses are good or bad."

The paper, "Acute stress increases monocyte levels and modulates receptor expression in healthy females," published March 9 in Brain, Behavior, and Immunity, was authored by Marcel van de Wouw, University of Calgary; Caitriona M. Long-Smith, Nathaniel L. Ritz, Gerard Moloney, Anne Marie Cusack, Kirsten Berding, Timothy G. Dinan and John F. Cryan, University College Cork; and Marzia Sichetti, University of Perugia.