Georgia State University. US: A new “trick” steroids use to suppress inflammation, which could be
used to make new anti-inflammatory drugs without the harmful side
effects of steroids, has been discovered by researchers at Georgia State
University. Their findings have been published in the journal Nature Communications.
Glucocorticoids, a class of steroid hormones, are among the most
commonly used anti-inflammatory agents. Steroids have been effective at
suppressing inflammation, but if used for long-term treatment they can
cause serious side effects such as increased risk of infections, liver
damage, fluid retention, increased blood pressure, weight gain, easy
bruising and slower wound healing.
There is an urgent need to develop novel anti-inflammatory strategies
to combat inflammation, which is the cause of many human diseases.
Inflammation has been linked to cancer, pulmonary diseases, infectious
diseases, neurological diseases, arthritis, otitis media (ear
infections) and obesity. It is the human body’s response to harmful
stimuli, such as pathogens or damaged tissues, but an overactive
response, too much inflammation, is detrimental and leads to disease. As
a result, inflammation must be tightly regulated.
“Chronic inflammatory diseases last for months and years, so you have to
have a medicine that can be used for treating inflammation for the long
term without having side effects,” said Dr. Jian-Dong Li, a lead investigator of the study and director of the Institute for Biomedical Sciences at Georgia State and also a Georgia Research Alliance Eminent Scholar.
It hasn’t been fully understood how glucocorticoids control
overactive inflammatory response, but this study found a previously
unknown, underlying mechanism that steroids use to suppress
inflammation. Scientists already knew that steroids suppress
inflammation by directly targeting nuclear factor-κB (NF-κB), a master regulator of pro-inflammatory mediators.
“We have found steroids also suppress inflammation by upregulating
IRAK-M, a key negative regulator of inflammatory pathways,” Li said.
The researchers found glucocorticoids tightly control
bacteria-induced innate immune and inflammatory response by enhancing
IRAK-M, one of the most critical negative feedback regulators of
inflammation that inhibits the activation of the proteins MyD88 and
IRAK1/4.
They propose that IRAK-M is a novel target of glucocorticoids to
suppress bacteria-induced inflammation. The study provides new insights
into the previously unidentified role of glucocorticoids in suppressing
inflammation by targeting the central bottleneck proteins MyD88 and
IRAK1/4.