Moderate-dose corticosteroid treatment improves patient recovery rates from sepsis

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 19^th, 2025, and will be published in  the Journal of Intensive Medicine.

Describing the motivation behind this research, Prof. 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.”

Prof. 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 Prof. 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 Prof. 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, Prof. 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.

Prof. 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.“

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Reference
DOI: 10.1016/j.jointm.2025.08.006

About IHU SEPSIS – Comprhensive Sepsis Center
The IHU SEPSIS is a hub of excellence dedicated to care, research, and training in pediatric and adult sepsis. It brings together 60 research teams from various disciplines—chemistry, physics, mathematics, engineering sciences, biology, medicine, social sciences and humanities, and economics—bringing together 275 researchers (including 117 female researchers and 41 junior researchers) and 94 clinical physicians (including 44 female clinicians).

The IHU SEPSIS has a threefold scientific ambition:

1. Better understand the host-pathogen interactions that transform an uncomplicated infection into sepsis, in order to identify signatures that characterize each patient's individual trajectory (endotype) and their response to a given treatment (treatable trait). The establishment of a prospective cohort and the PALETTE platform trial constitute a major asset for this characterization. 2. Develop, validate, and commercialize a rapid testing platform capable of performing more than 200 endotype and treatable trait analyses in two hours. These tools will enable the creation of a digital twin of organs and systems, designed to guide therapeutic choices in real time. An early decision, within six hours of the onset of symptoms, is crucial for successful treatment.

3. Design precision medicine, based on innovative therapeutic approaches: small molecules and nanomedicines, biotherapies (monoclonal antibodies, vaccines targeting pathogens or the immune system), and microbiota modulation strategies.

About University of Versailles Saint-Quentin-en-Yvelines – University Paris Saclay
Founded in 1991, the University of Versailles Saint-Quentin-en-Yvelines (UVSQ) is a public research university located in Paris, France. The university caters to over 19,000 students across its 5 campuses and 32 research laboratories. UVSQ has strong ties to the public hospital network in Paris. In addition to medicine and public health, research at UVSQ focuses on public policy, climate and sustainability, culture and heritage, and material sciences.

UVSQ is a member of University Paris Saclay, a consortium of educational and research institutions in and around Paris. The consortium houses over 8,000 researchers and serves over 50,000 undergraduate and graduate students.

Website: https://www.uvsq.fr/english

 https://www.universite-paris-saclay.fr/en

About Djillali Annane, Professor of Medicine at University of Versailles Saint-Quentin-en-Yvelines – University Paris Saclay
Prof. Djillali Annane is the director of IHU SEPSIS and of the General ICU at Raymond Poincaré Hospital and the Honorary Dean of the Medical School Simone Veil, UVSQ-UPS, and Guangci Professor of Shanghai Ruijin hospital, Shanghai Jiao Tong University School of Medicine

Prof. Annane has worked in the public hospital system in Paris since 1991 and completed his PhD in 1995 from Paris Descartes University. His areas of research are in Intensive care medicine, Cardiology, and Pharmacology, and he has contributed to over 710 research publications. In addition to his research work, Prof. Annane is the Chair of the Health Ministry Task Force against Sepsis and was the Chief Counsellor to the French Minister of Health from 2012 to 2017.

Funding information
This work was funded by the Programme Hospitalier de Recherche Clinique 2007 of the French Ministry of So- cial Affairs and Health (contract P070128), the Programme d’Investissements d’Avenir (ANR-18-RHUS-0004), France 2030 (IAHU-0004-PROMETHEUS), and the iRECORDS project, funded by ERA PerMed (JTC_2021) to Djillali Annane (ANR- 21-PERM-0005).