Treating Depression by Calming the Immune System
New study suggests that some cases of depression are tied to immune dysfunction.
Posted June 3, 2026 | Reviewed by Kaja Perina
Everyone gets depressed from time to time. Think about those unpleasant days when you’re sick. You feel depleted and unsociable. You lose interest in everything. You just want to crawl under the covers and rest alone.
Scientists call this “ sickness behavior ” and believe it evolved because it comes with benefits. Someone who isolates themselves from others is less likely to transmit their illness. A tired individual who loses interest in activities is diverting energy to fighting off a virus, or to healing.
But for about 332 million people worldwide , the depressive behavior usually reserved for recovering from an illness or injury never lets up, like a dark cloud that won’t vacate the sky. It raises an intriguing question: Could depression , or at least some instances of it, arise when the immune system doesn’t know when to quit?
Depression and the monoamine hypothesis
The cause of depression has long been mysterious, but astute medical observations in the 1950s suggested that moods are influenced by chemicals coursing through our brains. Doctors noticed that some patients taking a drug called reserpine for high blood pressure developed depressive symptoms. Conversely, tuberculosis patients taking a newly discovered antibiotic called iproniazid reported feelings of euphoria.
A decade later, the “ monoamine hypothesis ” was born. Reserpine and iproniazid were found to alter concentrations of monoamines, including serotonin, norepinephrine, and dopamine in the brain. These findings led to the development of Selective Serotonin Reuptake Inhibitors (SSRIs) like fluoxetine (Prozac).
While antidepressive drugs that target monoamine levels have been game changers for many suffering from severe depression, controversy still surrounds how and to what degree they work. For example, there are inconsistencies in monoamine levels and depressive symptoms, and the medications can take weeks to work . Most importantly, about one-third of depressive patients do not respond to this family of drugs .
What else could be at play?
The link between feeling sick and being depressed
In addition to associating brain chemicals with depressive states, researchers have found a strong connection with inflammation as well. Inflammation is a life-saving response when the body is injured or infected. It consists of a complex arsenal of biochemicals released by immune cells to fight off invading germs and repair damage.
But sometimes inflammation gets out of hand. Like friendly fire, overzealous inflammation puts normal healthy tissue in harm’s way. Some people experience sustained, or chronic, inflammation at low levels that, over time, can take a major toll on physical and mental health .
Clinical observations have bolstered the idea that mood disorders could be caused by an overreactive immune system, a concept that has been dubbed the “ inflammation hypothesis of depression .” People suffering from depression tend to have higher-than-normal inflammatory markers , such as cytokines like interleukin-6 (IL-6) and C-reactive protein (CRP).
The reverse is also true: people with chronic inflammatory conditions, such as arthritis or inflammatory bowel diseases, or severe infections, are at significantly higher risk of developing depression .
But until recently, hard evidence of mechanisms supporting these correlations has been scarce.
An anti-inflammatory medication reduced depression in a small trial
A new clinical trial published in May 2026 directly tested the inflammation hypothesis in patients unresponsive to standard antidepressants . Researchers at the University of Bristol administered tocilizumab to 14 of these patients and a placebo to 16 others and monitored their condition for a month.
Tocilizumab is a biologic drug typically prescribed for rheumatoid arthritis, an autoimmune disease. It is an antibody therapy that mitigates IL-6 activity, meaning that tocilizumab is an anti-inflammatory that dampens the immune response. The research team’s previous genetic analysis implicated excessive IL-6 as a potential culprit in depression .
The findings were striking. Patients who received tocilizumab “ generally showed greater improvement over time in several areas, including depression severity, fatigue, anxiety, and overall quality of life .” Even more promising, half of the participants given tocilizumab achieved depression remission.
There are some important limitations to this pilot study . The trial consisted of only 30 patients, which makes it difficult to draw firm conclusions about the safety and efficacy of this treatment for depression and whether it works in more diverse patient populations. The trial also treated and monitored patients for only four weeks, so it remains unclear whether the effects would be long-lasting.
Nonetheless, the promising preliminary findings warrant expansion of the study to larger patient groups, especially those who do not respond to monoamine drugs and have low-grade inflammatory markers in their blood.
What causes the inflammation that might cause depression?
If depression is the result of inflammation, as it appears to be in some cases, then the million-dollar question becomes: “What is causing this chronic, low-grade inflammation, and can it be fixed before it spirals into depression?”
A 2013 expert editorial reported the primary sources to be : “psychosocial stressors, poor diet , physical inactivity, obesity, smoking , altered gut permeability , atopy , dental cares [tooth decay/cavities], sleep and vitamin D deficiency.”
More recent studies show that environmental factors such as air pollution also belong on this list. Maintaining a healthy diet and routine exercise, with proper sleep and stress reduction practices, can go a long way in helping to prevent damaging inflammation that could lead to depression and other medical issues.
For more than 50 years, our thoughts about depression have largely been limited to what is going on inside the brain. This new study argues we need to expand our scope because the body and mind are inseparable.
It may be better to think of depression the way we think about cancer. Instead of having a single cause, depression may have multiple causes, both mental and physical. Such a framework opens new vistas for research and diversifies treatment options for patients.
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Bill Sullivan, Ph.D., is the author of Pleased to Meet Me: Genes, Germs, and the Curious Forces That Make Us Who We Are and a professor at the Indiana University School of Medicine.
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This article is part of the Bringwise Psychology Journal — daily insights on human behavior, mental health, and personal growth.