Antidepressants, such as Prozac, are routinely used to treat mental health issues, but recent research reveals they may also protect against major infections and life-threatening sepsis. Scientists at the Salk Institute have now discovered how medications regulate the immune system and protect against infectious disease, providing insights that could lead to a new generation of life-saving treatments and improve global readiness for future pandemics.
California
[US], February 16 (ANI): Antidepressants, such as Prozac, are routinely used to
treat mental health issues, but recent research reveals they may also protect
against major infections and life-threatening sepsis.
Scientists
at the Salk Institute have now discovered how medications regulate the immune
system and protect against infectious disease, providing insights that could
lead to a new generation of life-saving treatments and improve global readiness
for future pandemics.
The
Salk study follows recent findings that users of selective serotonin reuptake
inhibitors (SSRIs) like Prozac had less severe COVID-19 infections and were
less likely to develop long COVID.
Another
study found that Prozac--also known as fluoxetine--was effective in protecting
mice against sepsis, a life-threatening condition in which the body's immune
system overreacts to an infection and can cause multi-organ failure or even
death. By identifying a mechanism to explain fluoxetine's surprising
defence-boosting effects, Salk researchers have brought fluoxetine and
potentially other SSRIs closer to clinical testing for use against infections
and immune disorders.
"When
treating an infection, the optimal treatment strategy would be one that kills
the bacteria or virus while also protecting our tissues and organs," says
Professor Janelle Ayres, holder of the Salk Institute Legacy Chair and Howard
Hughes Medical Institute Investigator. "Most medications we have in our
toolbox kill pathogens, but we were thrilled to find that fluoxetine can
protect tissues and organs, too. It's essentially playing offense and defense,
which is ideal, and especially exciting to see in a drug that we already know
is safe to use in humans."
While
our immune systems do their best to protect us against infections, sometimes
they can overreact. In sepsis, the inflammatory response spins so out of control
that it starts damaging a person's own tissues and organs to the point of
failure. This same overreaction is also characteristic of severe COVID-19
illness.
An
obvious solution would presumably be to suppress the inflammatory response, but
doing so can actually make patients more vulnerable to their initial
infection--and more susceptible to new ones. Timing is also critical, as
immunosuppressive drugs need to be administered before any tissue damage has
taken place.
Instead,
an ideal treatment would 1) proactively control the intensity and duration of
the immune response to prevent any bodily damage and 2) kill the infection that
puts the body at risk to begin with.
To
understand what SSRIs might be doing in this context, the researchers studied mice
with bacterial infections and separated them into two categories: one
pretreated with fluoxetine and the other not. Excitingly, they saw the mice
pretreated with fluoxetine were protected from sepsis, multi-organ damage, and
death. The team then launched a series of follow-up experiments to make sense
of these effects.
First,
they measured the number of bacteria in each mouse population eight hours after
infection. Mice treated with fluoxetine had fewer bacteria at this stage,
signifying a less severe infection. The findings demonstrated that fluoxetine
had antimicrobial properties, which allowed it to limit bacterial growth.
Next,
the researchers measured the levels of different inflammatory molecules in each
group. They saw more anti-inflammatory IL-10 in their pretreated populations
and deduced that IL-10 prevented sepsis-induced hypertriglyceridemia--a
condition in which the blood contains too many fatty triglycerides. This
enabled the heart to maintain the proper metabolic state, protecting the mice
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
understand how fluoxetine's influence on serotonin levels might be contributing
to these effects, the researchers also looked at two new mouse populations:
Both were pretreated with fluoxetine, but one had circulating serotonin, while
the other did not. Circulating serotonin is a little chemical messenger that
travels your brain and body to regulate things like mood, sleep, and pain, and
is the main target for fluoxetine's mental health effects. They found that
fluoxetine's positive health outcomes were entirely unrelated to circulating
serotonin--regardless of whether the mice had serotonin in circulation, they
experienced the same infection defense 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 goes to show how much
more there is to learn about SSRIs."
Ayres and Gallant say their next step is to explore fluoxetine dosing regimens appropriate for septic individuals. They're also eager to see whether other SSRIs can have the same effects.
"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 dual protective and defensive effects in a
repurposed drug is really exciting." (ANI)
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