Your new experience awaits. Try the new design now and help us make it even better

REVIEW article

Front. Immunol.

Sec. Cytokines and Soluble Mediators in Immunity

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1682306

This article is part of the Research TopicCytokines in inflammatory, infectious and noninfectious diseasesView all 7 articles

Cytokines in Sepsis: A Critical Review of the Literature on Systemic Inflammation and Multiple Organ Dysfunction

Provisionally accepted
Roberta VellaRoberta Vella1*Diego PanciDiego Panci2Francesco CariniFrancesco Carini3Ginevra MaltaGinevra Malta4SALVATORE VIENISALVATORE VIENI1Sabrina DavidSabrina David3Giuseppe Davide AlbanoGiuseppe Davide Albano4Maria PuntarelloMaria Puntarello4Stefania ZerboStefania Zerbo4Antonina ArgoAntonina Argo4
  • 1Universita degli Studi di Palermo Dipartimento di Medicina di Precisione in Area Medica Chirurgica e Critica, Palermo, Italy
  • 2Universita degli Studi di Palermo, Palermo, Italy
  • 3Universita degli Studi di Palermo Dipartimento di Biomedicina Neuroscienze e Diagnostica avanzata, Palermo, Italy
  • 4Universita degli Studi di Palermo Dipartimento di Promozione della Salute Materno Infantile di Medicina Interna e Specialistica di Eccellenza G D'Ales, Palermo, Italy

The final, formatted version of the article will be published soon.

Select one of your emails

You have multiple emails registered with Frontiers:

Notify me on publication

Please enter your email address:

If you already have an account, please login

You don't have a Frontiers account ? You can register here

Sepsis constitutes a profoundly heterogeneous and dynamic clinical syndrome, precipitated by a maladaptive host response to infection in which the immune system's regulatory balance is fundamentally disrupted. The intricate interplay between proinflammatory and anti-inflammatory pathways, ordinarily responsible for maintaining immune homeostasis, becomes pathologically skewed. Within this altered immunological landscape, cytokines serve as pivotal mediators, orchestrating a cascade of cellular events that may culminate in a rapid transition from systemic hyperinflammation to a state of immune exhaustion or suppression. This review offers a critical synthesis of the current scientific literature on the immunopathogenesis of sepsis, with a particular emphasis on the molecular and cellular mechanisms governing cytokine regulation. Special attention is directed toward elucidating the contribution of these mediators to the onset and progression of multiorgan dysfunction syndrome (MODS), a central and often fatal complication of severe sepsis. Through an integrative examination of the principal immune signaling networks and pathophysiological processes involved in sepsis, this review provides a cohesive theoretical framework positioning immune dysregulation as the fundamental axis of clinical deterioration. Such an approach

Keywords: sepsis1, cytokines2, inflammation3, multiple organ dysfunction4, immunity5

Received: 08 Aug 2025; Accepted: 16 Sep 2025.

Copyright: © 2025 Vella, Panci, Carini, Malta, VIENI, David, Albano, Puntarello, Zerbo and Argo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Roberta Vella, roberta.vella02@unipa.it

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material