PAMPs, DAMPs e Tempestade de Citocinas na Sepse: Uma Revisão da Imunopatogênese da Disfunção Endotelial e Orgânica

Abstract

This article reviews recent scientific literature on the immunological mechanisms underlying the cytokine storm in sepsis, focusing on the relationship between dysregulated immune activation, endothelial injury, and multiple organ dysfunction. The research was conducted through a comprehensive bibliographic search in national and international databases, including original studies and review articles addressing interactions among PAMPs, DAMPs, and pattern-recognition receptors, as well as key signaling pathways such as NF-κB, MAPKs, the NLRP3 inflammasome, and ubiquitination processes. The evidence analyzed demonstrates that the excessive release of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, triggers microcirculatory disturbances, increased vascular permeability, NET formation, and pro-coagulant activation, contributing to progressive tissue injury and organ failure. Concurrently, the overactivation of anti-inflammatory mediators such as IL-10 may lead to immunosuppression and increased susceptibility to secondary infections, highlighting the biphasic and heterogeneous nature of sepsis. This review also discusses emerging therapeutic strategies aimed at modulating this immunological imbalance, including extracorporeal cytokine-removal therapies, interventions targeting intracellular signaling pathways, and innovative approaches such as plasma gelsolin supplementation. Understanding these processes is essential for improving diagnostic accuracy, identifying immune phenotypes, and developing more precise therapeutic interventions capable of reducing the morbidity and mortality associated with sepsis.

Keywords: Sepsis; Cytokine storm; Endothelium; Inflammation; Multiple organ dysfunction.