Understanding how omega-3
dampens inflammatory reactions
The Norwegian
University of Science and Technology (NTNU)
Omega-3 fatty acids,
which we primarily get through eating fatty fish, have long been thought to be
good for our health.
Many dietary studies have suggested that high intake is
associated with a reduced risk of various disorders.
Clinical trials have also shown
beneficial anti-inflammatory effects in patients taking omega-3 supplements.
Recent research from
NTNU supports previous discoveries, and has also found new, useful effects of
omega-3 supplements and how these lipids dampen harmful inflammatory reactions
in the body.
Despite numerous
published dietary and clinical studies, we still don't fully understand how
omega-3 fatty acids affect our cells and if this varies from person to person,
between healthy and ill individuals, or whether the mechanism of action varies
in different tissues and cells.
What we are most sure of is that omega-3 fatty
acids can dampen inflammatory reactions.
Inflammatory reactions are very
important in combating infections, but they can be harmful if activated too
strongly or in the absence of bacteria and viruses, like in autoimmune diseases
and organ transplants.
Macrophages, which are
immune cells that live in all tissues and organs, play a key role in
coordinating inflammatory reactions in the body and monitor everything that
happens in our tissues.
The macrophages convert the information they obtain
through various sensors or receptor on their surface to secretion of various
hormone-like signal substances that control all parts of inflammatory
reactions.
Inflammation can be
harmful
We have increasingly
become aware that macrophages can be more or less potent in activating
inflammatory reactions. So-called sterile inflammatory reactions, such as
autoimmune diseases, are often directly harmful.
The ability of
macrophages to stimulate inflammatory reactions depends on processes within the
macrophage.
Autophagy is one of
the processes within macrophages that is important for whether a macrophage is
calm or hyperactive. Autophagy (meaning "self-eating") is a key process
for degradation of dysfunctional or unnecessary proteins and other components
within our cells.
In the last few years,
we've learned a lot about how important this process is, say the researchers.
The Nobel Prize in Physiology or Medicine 2016 was given to Yoshinori Ohsumi
for his discovery of the key genes that control autophagy.
Autophagy is
constantly going on in all cells and increases if the cells are starving or
injured. We hypothesized that omega-3 fatty acids could dampen inflammatory
reactions by elevating autophagy in macrophages. If so, we surmised that this
effect might change the signal transformation in the macrophage and as a
result, suppress activation of inflammatory reactions.
Activates
self-cleaning process
By studying
macrophages isolated from mice and humans, we found that the omega-3 fatty
acids activated the autophagy and specifically affected some proteins that
transform the signals from the environment.
Furthermore, we found that omega-3
fatty acids dampened many inflammatory mechanisms within the macrophages, but
especially reduced what is known as the type 1 interferon response.
The factor CXCL-10,
which macrophages secrete as part of this interferon response following many
types of stimuli, was the most clearly reduced factor after adding omega-3 to
the cells.
We then examined blood
samples from a clinical study in cardiac transplant patients where we knew that
omega-3 supplements improved their clinical status. In these cases, we found
that omega-3 fatty acids reduced the level of CXCL-10.
Supplements beneficial
Autophagy thus changes
in macrophages in response to omega-3 fatty acids and specifically inhibits the
secretion of inflammatory factors that belong to the interferon response, with
CXCL-10 showing the clearest reduction.
The results of this study are being
published in the journal Autophagy.
These findings
indicate that omega-3 fatty acid supplements may be particularly beneficial in
patients who have conditions that are driven or aggravated by a strong
interferon response and CXCL-10.
Our research group
hopes that this one day will benefit patients with different forms of cancer,
meningitis, multiple sclerosis, Alzheimer's disease or jaundice. But we must
emphasize that a lot of work remains.
