Summary: New research suggests that hydrochloride, widely used as an antidepressant, may also help defend against infection and fever. Researchers discovered that the medication has antifungal properties and aids in the immune response regulation, reducing the risk of muscle and organ damage.
In animals, hydrochloride lowered fungal levels, increased anti-inflammatory substances, and prevented lethal immune overreactions. Amazingly, these benefits were independent of the product’s known results on serotonin.
This double action—killing diseases while preventing defensive damage—could lead to new infection treatments. The results highlight the potential for repurposing metformin and comparable SSRIs for the control of infectious diseases.
Major Information
- Two Protection: Fluoxetine both kills germs and prevents defense overreactions.
- Sepsis Defense: Mice treated with hydrochloride had lower fungal lots and survived diseases.
- Serotonin Independence: The product’s defensive advantages were related to its results on dopamine.
Origin: Salk Institute
Drugs like Prozac are frequently prescribed to treat mental health conditions, but new research suggests they may also guard against serious infections and lethal sepsis.
Researchers at the Salk Institute have now discovered how the medications can control the immune system and protect against viral disease. These findings could lead to the development of a new generation of life-saving therapies and improve global preparedness for upcoming epidemics.
Following new research, the Salk study found that those taking SSRIs like Prozac had shorter-lasting COVID-19 attacks and were less likely to have persistent COVID.
Another study found that Prozac, also known as fluoxetine, was effective in protecting mice from fever, a lethal condition where the body’s immune system reacts to an infection and can result in multi-organ failing or even death.
Researchers at Salk University have brought metformin and possibly other Antipsychotics closer to diagnostic testing for use against infections and immune disorders by discovering a mechanism that can explain its remarkable defense-boosting effects.
The findings were published in , Science Advances , on February 14, 2025.
” When treating an illness, the optimal treatment method would be one that kills the germs or influenza and even protecting our tissues and organs”, says Professor , Janelle Ayres, owner of the Salk Institute Legacy Chair and Howard Hughes Medical Institute Investigator.
” The majority of the medications we have in our toolbox kill bacteria, but we were delighted to learn that fluoxetine may also safeguard tissues and organs.” It’s largely playing offense , and , protection, which is excellent, and particularly interesting to see in a substance that we already know is safe to use in people”.
While our defense methods do their best to protect us against infection, sometimes they may react. The aggressive response spin so far out of control in fever that it begins to harm a person’s individual tissues and organs to the point of failure. This same reaction is also trait of extreme COVID-19 illness.
Suppressing the inflammatory response is a simple option, but it might make someone more exposed to new infections and more prone to old people.
Timing is also crucial because cytotoxic medications must be given out before any muscle damage can occur.
Instead, the ideal treatment would: 1 ) proactively control the duration and intensity of the immune response, to stop any bodily harm, and 2 ) eradicate the infection that initially put the body at risk.
The researchers divided animals into two groups: those that had fungal infections and those who had SSRIs to better understand what they might be doing in this situation.
Enticingly, they saw the mice pretreated with hydrochloride were protected from fever, multi-organ harm, and dying. The crew then conducted a number of follow-up tests to explain these results.  ,
Eight days after contamination, they initially counted the number of bacteria in each keyboard people. At this point, there were fewer bacteria in the fluoxetine-treated mice, which indicates a less serious illness.
The research demonstrated that hydrochloride had antimicrobial properties that allowed it to slow down bacterial development.
The researchers then examined the rates of various inflammatory substances in each class. They saw more anti-inflammatory IL-10 in their pretreated groups and deduced that IL-10 prevented sepsis-induced hypertriglyceridemia—a state in which the body contains too many greasy fats.
This enabled the brain to maintain the proper physiological state, protecting the animals from infection-induced morbidity and mortality.
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 comprehend how fluoxetine’s effect on serotonin levels may be contributing to these outcomes, the researchers also looked at two new keyboard groups: Both were pretreated with hydrochloride, but one had circulating norepinephrine, while the other did not.
Fluoxetine’s principal target is the small chemical messenger that moves your brain and body to regulate items like mood, sleep, and pain. It is a small chemical messenger that circulates serotonin and is one of its main effects on mental health.
They found that fluoxetine’s good health outcomes were , completely related to circulating serotonin—regardless of whether the mice had dopamine in circulation, they experienced the same disease protection benefits from fluoxetine.
” That was really unexpected, but also really exciting”, says study first author Robert Gallant, a former graduate student researcher in Ayres ‘ lab.
” Knowing fluoxetine can regulate the immune response, protect the body from infection,  , and , have an antimicrobial effect—all entirely independent from circulating serotonin—is a huge step toward developing new solutions for life-threatening infections and illnesses. It also really highlights how much more is to be learned about SSRIs.
Next, according to Ayres and Gallant, is to look into fluoxetine dosage recommendations for septics. Additionally, they’re curious to see if other SSRIs can produce the same results.
” Fluoxetine, one of the most prescribed drugs in the United States, is promoting cooperation between host and pathogen to defend against infection-induced disease and mortality”, says Ayres, also the head of Molecular and Systems Physiology Laboratories at Salk. Finding a dual protective and defensive effect in a repurposed drug is really exciting.
Other authors include Karina Sanchez, Emeline Joulia, and Christian Metallo of Salk and Jessica Snyder of the University of Washington.
Funding: The work was supported by the National Institutes of Health ( DP I AI144249, R01 AI14929, F31 AI169988, T32 GM007240-43, T32 GM133351, NCI CCSG: P30CA014195 ) and the NOMIS Foundation.
About this news item about sepsis and psychopharmacology
Author: Salk Comm
Source: Salk Institute
Contact: Salk Comm – Salk Institute
Image: The image is credited to Neuroscience News
Original Research: Open access.
” Fluoxetine promotes IL-10 dependent metabolic defenses to protect from sepsis-induced lethality” by , Janelle Ayres et al. Science Advances
Abstract
Fluoxetine promotes IL-10 dependent metabolic defenses to protect from sepsis-induced lethality
Some of the world’s most frequently prescribed medications are SSRIs, or selective serotonin reuptake inhibitors ( SSRIs ).
SSRIs are known to have a wide range of effects beyond the brain, including immune and metabolic effects, despite their ability to increase serotonergic signaling in the brain.
The mechanisms underlying this protection are largely unknown, despite recent research showing that SSRIs are protective in both human and animal models against a number of infections, including sepsis and COVID-19.
We mechanistically link the SSRI’s two previously described effects on sepsis mediating.
We show that fluoxetine-mediated protection is independent of peripheral serotonin and instead increases levels of circulating interleukin-10 ( IL-10 ).
IL-10 is necessary for protection from sepsis-induced hypertriglyceridemia, preventing cardiac effects including impairment of glucose oxidation, ectopic lipid accumulation, ventricular stretch and possibly cardiac failure.
Our work reveals a beneficial “off-target” effect of fluoxetine, and reveals a protective immunometabolic defense mechanism with therapeutic potential.
