While our immune systems typically do a great job containing pathogens and clearing infections, they can occasionally overreact. When the immune response to infection becomes excessive, it causes rapid, widespread organ damage in a life-threatening condition called sepsis. Worldwide, sepsis imposes significant social, economic, and health costs. Estimates put global cases of sepsis at 50 million per year, resulting in over 11 million deaths annually.
Global efforts to limit sepsis cases are largely focused on containing the spread of pathogens and rapid treatment of infections. However, the only established treatment once sepsis sets in is the use of corticosteroids that modulate the immune response. These drugs reduce the damage that the immune system inflicts on organs and allow them to heal.
A team of researchers from France, led by professor Djillali Annane from IHU SEPSIS Comprehensive Sepsis Center at the Raymond Poincaré Hospital, APHP University Versailles Saint Quentin–University Paris Saclay, has examined the various mechanisms by which corticosteroids limit sepsis-related damage to the body. Their findings and recommendations were made available online on September 19th, 2025, and will be published in the Journal of Intensive Medicine.
Describing the motivation behind this research, Annane says, “Although international guidelines have helped reduce crude mortality rates from sepsis, there are still no specific therapies other than corticosteroids. Our objectives were to provide the most recent data on corticosteroids, as well as up-to-date evidence regarding their effects in patients with sepsis.”
Annane’s team reviewed nearly 100 research articles that studied the various effects of corticosteroids against symptoms of sepsis. They found that corticosteroids worked by stabilizing the mitochondria in dysfunctional immune cells, as well as switching these cells away from releasing molecules that increased inflammation to those that decreased inflammation. Corticosteroids also lowered the release of molecules causing unregulated cell death (necrosis). These changes, in turn, reduced the stress on other tissues and organs and ultimately helped improve sepsis.
In addition, corticosteroids had protective functions on the heart and vascular system before and during the progression of sepsis. They prevented the dilation of blood vessels and restored responsiveness to norepinephrine, both of which are crucial mechanisms to prevent blood pressure from becoming dangerously low.
The team then cite many studies that show the benefits of high-dose corticosteroid treatments against sepsis in clinical settings. The evidence is unambiguous—high dosages of corticosteroids reduce the risk of cardiovascular failure and other kinds of organ failure, inhibit inflammation, and reduce the length of hospital stay needed to recover from sepsis.
However, as Annane points out, there are some risks associated with using corticosteroids to treat sepsis. “There was moderate to high certainty of an increased risk of elevated glucose and sodium levels in the blood. Furthermore, use of corticosteroids during the recent coronavirus disease (COVID-19) pandemic appears to have been associated with an increased risk of opportunistic infections,” he says. In Annane’s opinion, future research should focus on accurately identifying which patients will benefit most from corticosteroid treatment and which ones may experience harmful effects from these drugs.
Based on their analysis, Annane’s team has made a decision tree that clinicians can follow if they suspect that a patient has sepsis.
If sepsis results from COVID-19 or some other viral respiratory infection, start treatment with dexamethasone
If sepsis is from bacterial pneumonia, start treatment with hydrocortisone. Add fludrocortisone if the patient goes into septic shock.
Specifics of the treatment will depend on patient history and disease progression.
Annane concludes by observing that, “the use of moderate doses of corticosteroids for a week or two in patients with sepsis is supported by biological and pharmacological rationale, evidence from clinical trials, and high-quality systematic reviews and meta-analyses, as well as clinical practice guidelines.“
Source: IHU SEPSIS Comprehensive Sepsis Center