How antidepressants prevent infection and sepsis

Antidepressants are prescribed universally to treat mental health disorders, but new research suggests they can also prevent severe infections and life-threatening sepsis. Scientists at the Salk Institute have now discovered how these drugs can regulate the immune system and defend against infectious diseases, which could lead to a new generation of life-saving treatments and enhance global preparation for future pandemics.

Recent findings from the SALK study are that users of selective serotonin reuptake inhibitors (SSRIS) such as Prozac have a more severe Covid-19 infection and are unlikely to develop prolonged covid. Another study found that Prozac (also known as fluoxetine) effectively protects mice from sepsis, a life-threatening disease in which an overreaction of the body’s immune system can lead to infection. And it can lead to multiple organ failure or even death. By identifying a mechanism that explains the surprising defense effects of fluoxetine, Salk researchers brought fluoxetine and potential other SSRIs to close clinical testing to fight infection and immune diseases.

The survey results are published in Science Advances February 14, 2025.

“When treating infections, the best treatment strategy will also be a strategy to kill bacteria or viruses while protecting our tissues and organs,” said Professor Janelle Ayres, chairman of Salk Institute Legacy and Howard Hughes Medical Institute investigator. “We are in the Tools Most drugs used in the box kill pathogens, but we are happy to find that fluoxetine can also protect tissues and organs. It is attacking by nature and Defense, which is ideal, and especially exciting, is that we already know the drugs that are safe to use in humans. ”

While our immune system tries to protect us from infection, sometimes they can overreact. In sepsis, the inflammatory response rotates so out of control that it begins to damage a person’s own tissues and organs to the point of failure. The same overreaction is also a characteristic of severe Covid-19 disease.

An obvious solution is probably to suppress the inflammatory response, but doing so can actually make the patient more susceptible to the initial infection and more susceptible to new infections. Time is also crucial because immunosuppressive drugs are required before any tissue damage occurs.

Instead, ideal treatments are 1) proactively controlling the intensity and duration of the immune response to prevent any personal damage, and 2) killing infections that put the body at risk.

To understand what SSRI might do in this case, the researchers looked at mice with bacterial infections and divided them into two categories: one pretreated with fluoxetine and the other without fluoxetine Preprocessing. Excitingly, they saw mice pretreated with fluoxetine protected by sepsis, multiple organ damage and death. The team then embarked on a series of follow-up experiments to understand the effects.

First, they measured the number of bacteria in each mouse population eight hours after infection. At this stage, mice treated with fluoxetine had fewer bacteria, suggesting that the infection was less severe. The results of the study show that fluoxetine has antibacterial properties, thus limiting bacterial growth.

Next, the researchers measured the levels of different inflammatory molecules in each group. They saw more anti-inflammatory IL-10 in the pretreated population and deduced that IL-10 prevented sepsis-induced hypertriglyceridemia, in which case the blood contains too much fat Triglycerides. This allows the heart to maintain a proper metabolic state, thus protecting mice from morbidity and mortality caused by infection.

The team decoupled this IL-10-dependent protection from multi-organ damage and death from their earlier discovery of fluoxetine’s antimicrobial effects, in turn revealing the drug’s dual-purpose potential to 1) kill pathogens and 2) alleviate infection-induced damage to the Body.

To understand the possible effects of fluoxetine on serotonin levels, the researchers also studied two new mouse populations: both were pretreated with fluoxetine, but one circulated serotonin per capita, while the other One is not. Circulating serotonin is a chemical messenger that spreads your brain and body to regulate things like mood, sleep, and pain, and is a major target for fluoxetine’s mental health effects. They found that the positive health outcomes of fluoxetine were Completely irrelevant to circulating serotoninRegardless of whether the mice have serotonin in the circulation, they will get the same infection defense benefits from fluoxetine.

“It’s really unexpected, but it’s really exciting,” said Robert Gallant, first author of the study. “Knowing that fluoxetine regulates immune responses and protects the body from infection, and Has antibacterial effects – completely independent of circulating serotonin, a big step towards developing new solutions for life-threatening infections and diseases. This does also indicate that more information about SSRI is needed. ”

Ayres and Gallant said their next step is to explore fluoxetine dose regimens suitable for septic tank individuals. They also want to see if other SSRIs will have the same effect.

“Fluoxetine is one of the drugs prescribed in the United States and is promoting collaboration between host and pathogen to defend against disease and mortality caused by infection,” said Ayres, also head of the Salk Molecular and Systems Physiology Laboratory. “It’s really exciting to find dual protection and defense effects in reused drugs.”

Other authors include Karina Sanchez, Emeline Joulia and Christian Metallo of Salk and Jessica Snyder of the University of Washington.

This work was obtained by the National Institutes of Health (DPI AI144249, R01 AI14929, F31 AI169988, T32 GM007240-43, T32 GM1333351, NCI CCSG: NCI CCSG: P30CA014195) and NOMIS Foundation.