Cytokine storm in severe bacterial infections: A Mini-Review of molecular insights and treatment strategies.

Cytokine storm (CS) is a severe hyperinflammatory syndrome characterized by the excessive production of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α. While CS can arise from various triggers, including viral infections, autoimmune disorders, and immunotherapies, in severe bacterial infections and sepsis, it is primarily initiated by bacterial pathogen-associated molecular patterns (PAMPs). This dysregulated immune response increases the risk of endothelial dysfunction, disseminated intravascular coagulation, acute respiratory distress syndrome, multi-organ failure, and mortality. This mini-review elucidate the molecular and cellular processes of CS in severe bacterial infections, focusing on key pathogenes like Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. We narratively reviewed peer-reviewed publications published from 2020 to 2025, indexed in PubMed, Web of Science, and Google Scholar, prioritizing studies on bacterial sepsis and hyperinflammation while excluding viral-only, autoimmune, or non-relevant reports. Bacterial PAMPS stimulate innate immune receptors (e.g., Toll-like receptors, NOD-like receptors, and inflammasomes), leading to prolonged NF-κB and STAT signaling, excessive cytokine release, and amplification by interactions among macrophages, neutrophils, dendritic cells, and adaptive immune cells. Genetic polymorphisms and epigenetic modifications (e.g., DNA methylation changes in IL-10, IL-1β, and TNF-α promoters) further modulate severity. Therapeutic approaches, including corticosteroids, immunomodulatory antibiotics, JAK inhibitors, mesenchymal stem cells, nanoparticle delivery, and biomarker-guide approaches show promise but face challenges from patient variability and safety concerns. A deeper understanding of these pathways is crucial for developing targeted, and personalized therapy strategies to reduce morbidity and mortality in bacterial sepsis.