Immune response in sepsis as a target: which options? 

Throughout the history of medicine, sepsis has consistently challenged caregivers. The discovery of antibiotics brought significant advances in treating sepsis, but germ theory did not fully explain the pathogenesis of sepsis: many patients with sepsis still died even if antibiotic treatment had successfully killed off the pathogen that caused it. Now we understand that the dysregulated response of the host, not the germ, drives the pathogenesis of sepsis. (1) In 2016, the Sepsis-3 Task Force on Sepsis defined sepsis as a life-threatening organ dysfunction arising from a dysregulated host response to infection. This shifted clinical and research from focusing only on infection to seeing the host response as a central therapeutic target. (2) Physicians once viewed sepsis primarily as an overwhelming inflammatory condition driven by excessive cytokine release. However, it is now recognised as a complex dysregulated immune response involving both hyperinflammation and prolonged immune suppression, including lymphopenia and immunoparalysis. While earlier therapeutic strategies focused primarily on controlling inflammation, research is increasingly exploring how sepsis-induced immune dysfunction contributes to secondary and opportunistic infections, and whether immune-targeted therapies can improve outcomes in selected patients. (3) 

In our lightning talk, “Immune response in sepsis as a target: which options?” the speakers will describe new therapeutic options in septic patients targeting the immune response, offer options in how to tailor treatment strategies for specific patient categories such as those with immunoparalysis or oncology-related sepsis, and highlight how to stratify patients based on their risk of developing opportunistic infections. Lightning talks are exciting and informative. Each speaker must be direct and to the point, as they only have 10 minutes to make their case.  

Mervyn Singer, Professor of Intensive Care Medicine at University College London, UK, will deliver the first talk, entitled: “Steroids: why, when, how?”. Prof. Singer is a leading authority on sepsis pathophysiology. He was a co-chair of the Sepsis-3 Task Force and one of the lead authors of the rationale, development, and validation of the Sequential Organ Failure Assessment (SOFA)-2 Score. (4)(5) Accompanying evidence from the latest studies, Prof. Singer will review the rationale for steroids, efforts to identify those patients who will (or won’t) benefit, and cover the challenges of selecting optimal dosing regimens and duration. 

Dr. Giorgia Montrucchio, an intensivist at the Città della Salute e della Scienza Hospital and the University of Turin, Italy, will deliver the second talk, “Adjuvant Therapeutic Plasma Exchange in Septic Shock”. She is a co-author of an Italian multidisciplinary consensus document on adjunctive immunotherapeutic agents in sepsis and septic shock, which evaluated the evidence for, among others, corticosteroids, intravenous immunoglobulins, and other novel immunotherapeutic agents in septic patients. (6) She will present the current evidence, including practical implementation and patient selection criteria for therapeutic plasma exchange (TPE), which shows significant potential in eliminating circulating injurious mediators in a short intervention while simultaneously replacing essential but already-consumed protective plasma proteins. (7) 

The next speaker is Dr. Krisztina Madách from the Department of Anaesthesiology and Intensive Therapy at Semmelweis University in Budapest, Hungary. Her research focuses on sepsis and genetic predisposition, with her group’s latest prospective work linking genetic variants directly to organ dysfunction and septic shock. (8) In her talk, “Immunoparalyzed patients: new treatments?”, she will bring into focus the question of why patients who survive the initial cytokine storm of sepsis die later from secondary infections due to immunoparalysis. To address this, she will explore the complex cellular and microbiological mechanisms of this condition, the possibilities of patient stratification based on validated biomarkers, and the evolving landscape of precision immunotherapy, including cytokines, growth factors, checkpoint inhibitors, and microbiome restoration. 

Our final lightning talk, “Haematological and cancer patients: a specific target?” will come from one of the world’s leading authorities on critical illness in immunocompromised patients. Prof. Elie Azoulay is currently Professor of Medicine at Paris-Cité University and Director of the Intensive Care Department at Hôpital Saint-Louis and served as President of ESICM from 2022 to 2024. He is the current Editor-in-Chief of Critical Care: Sepsis and Severe Infection. Prof. Azoulay founded the GRRR-OH (Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique) network in 2004, linking over 30 ICUs in France which subsequently expanded internationally through the Nine-i (Caring for Critically Ill Immunocompromised Patients) network. In his talk, he will discuss how haematological and cancer patients can uniquely benefit from tailored sepsis management. He will highlight the specific challenges in treating patients with haematological malignancies, especially their key vulnerabilities, innovations in management contributing to improved outcomes, and how evidence points to the benefit of a targeted approach. (9)(10)(11) 

The lightning talk “Immune response in sepsis as a target: which options?” will take place at the Euroanaesthesia Congress 2026 on Sunday, June 7 at 11:00 – 12:00 CEST in room PORT A. 

References 

1. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369(9):840-51. doi: 10.1056/NEJMra1208623. Erratum in: N Engl J Med. 2013 Nov 21;369(21):2069. PMID: 23984731. https://www.nejm.org/doi/10.1056/NEJMra1208623#  

2. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287. PMID: 26903338; PMCID: PMC4968574. https://jamanetwork.com/journals/jama/fullarticle/2492881  

3. Silva EE, Skon-Hegg C, Badovinac VP, Griffith TS. The Calm after the Storm: Implications of Sepsis Immunoparalysis on Host Immunity. J Immunol. 2023;211(5):711-719. doi:10.4049/jimmunol.2300171 https://academic.oup.com/jimmunol/article/211/5/711/7927378 

4. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287. PMID: 26903338; PMCID: PMC4968574. https://jamanetwork.com/journals/jama/fullarticle/2492881  

5. Ranzani OT, Singer M, Salluh JIF, et al. Development and Validation of the Sequential Organ Failure Assessment (SOFA)-2 Score. JAMA. 2025;334(23):2090–2103. doi:10.1001/jama.2025.20516 https://jamanetwork.com/journals/jama/fullarticle/2840822 

6. Girardis M, Coloretti I, Antonelli M, Berlot G, Busani S, Cortegiani A, De Pascale G, De Rosa FG, De Rosa S, Donadello K, Donati A, Forfori F, Giannella M, Grasselli G, Montrucchio G, Oliva A, Pasero D, Piazza O, Romagnoli S, Tascini C, Viaggi B, Tumbarello M, Viale P. Adjunctive immunotherapeutic agents in patients with sepsis and septic shock: a multidisciplinary consensus of 23. J Anesth Analg Crit Care. 2024 Apr 30;4(1):28. doi: 10.1186/s44158-024-00165-3. PMID: 38689337; PMCID: PMC11059820. https://link.springer.com/article/10.1186/s44158-024-00165-3  

7. Sauer A, Stahl K, Seeliger B, et al. The effect of therapeutic plasma exchange on the inflammatory response in septic shock: a secondary analysis of the EXCHANGE-1 trial. Intensive Care Med Exp. 2025;13(1):18. Published 2025 Feb 14. doi:10.1186/s40635-025-00725-z https://link.springer.com/article/10.1186/s40635-025-00725-z 

8. Madách K, Aladzsity I, Szilágyi A, et al. 4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study. Crit Care. 2010;14(2):R79. doi:10.1186/cc8992 https://link.springer.com/article/10.1186/cc8992  

9. Azoulay E, Mokart D, Pène F, Lambert J, Kouatchet A, Mayaux J, Vincent F, Nyunga M, Bruneel F, Laisne LM, Rabbat A, Lebert C, Perez P, Chaize M, Renault A, Meert AP, Benoit D, Hamidfar R, Jourdain M, Darmon M, Schlemmer B, Chevret S, Lemiale V. Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium–a groupe de recherche respiratoire en réanimation onco-hématologique study. J Clin Oncol. 2013 Aug 1;31(22):2810-8. doi: 10.1200/JCO.2012.47.2365. Epub 2013 Jun 10. PMID: 23752112. https://ascopubs.org/doi/10.1200/JCO.2012.47.2365?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed 

10. Nates JL, Pène F, Darmon M, Mokart D, Castro P, David S, Povoa P, Russell L, Nielsen ND, Gorecki GP, Gradel KO, Azoulay E, Bauer PR; Nine-I Investigators. Septic shock in the immunocompromised cancer patient: a narrative review. Crit Care. 2024 Aug 30;28(1):285. doi: 10.1186/s13054-024-05073-0. PMID: 39215292; PMCID: PMC11363658. https://link.springer.com/article/10.1186/s13054-024-05073-0  

11. Azoulay E, Zafrani L, Nates J, Maillard A, Chean D, Ferreyro B, Nelson JE, Bauer PR, Puxty K, Gutierrez C, Bigé N, Mariotte E, Valade S, Boell B, Puntillo K, Lafarge A, Soares M, Schellongowski P, Canet E, Castro P, Demoule A, Pène F, Munshi L, Shimabukuro-Vornhagen A, Staudinger T, Russell L, Fernandez S, Kochanek M, Lemiale V, von Bergwelt-Baildon M, Darmon M, Martin-Loeches I. Advances in the critical care management for patients with hematological malignancies. Blood Rev. 2025 Nov;74:101306. doi: 10.1016/j.blre.2025.101306. Epub 2025 Jun 1. PMID: 40603200. https://www.sciencedirect.com/science/article/abs/pii/S0268960X25000517?via%3Dihub