biostudies-literatureWang YShanghai's Science and Technology Innovation Action Plan International Science and Technology Cooperation ProjectShanghai Municipal Health Commission Research Project Funde01104https://www.ebi.ac.uk/biostudies/studies/S-EPMC12499386biostudies-literatureUnknown12(37)Fatal jellyfish stings often cause multi-organ failure. Until now, these fatal outcomes are attributed to the direct toxic effects of the venom. Here, a mouse model of delayed jellyfish envenomation syndrome (DJES) is established and showed that venom from Nemopilema nomurai jellyfish can trigger a deadly cytokine storm - a severe inflammatory reaction. Mice injected with the venom displayed acute multi-organ failure and significant upregulation of over 20 pro-inflammatory cytokines (including IL-6, TNF-α, CXCL2, and CCL4) in the heart, liver, and kidneys. Transcriptomic analyses identified NF-κB p65 subunit activation as central to the cytokine storm induction. Knockdown of p65 in macrophages reduced cytokine production and improved cell viability. Treatment with dexamethasone, an NF-κB iAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Cytokine Storm Induction Linked to Multi-Organ Failure in Fatal Jellyfish Stings.PMC1249938620224014424410710100Chen JGeng XZhang JChen LHou XYang FLv JXiao LSun QLin HLiu CYan BWang YfalseCytokine Storm Induction Linked to Multi-Organ Failure in Fatal Jellyfish Stings.Fatal jellyfish stings often cause multi-organ failure. Until now, these fatal outcomes are attributed to the direct toxic effects of the venom. Here, a mouse model of delayed jellyfish envenomation syndrome (DJES) is established and showed that venom from Nemopilema nomurai jellyfish can trigger a deadly cytokine storm - a severe inflammatory reaction. Mice injected with the venom displayed acute multi-organ failure and significant upregulation of over 20 pro-inflammatory cytokines (including IL-6, TNF-α, CXCL2, and CCL4) in the heart, liver, and kidneys. Transcriptomic analyses identified NF-κB p65 subunit activation as central to the cytokine storm induction. Knockdown of p65 in macrophages reduced cytokine production and improved cell viability. Treatment with dexamethasone, an NF-κB i2025-01-01T00:00:00Z2025 Oct2026-06-04T04:43:33.72Z2026-05-05T03:12:21.621ZS-EPMC124993864065378210.1002/advs.202501104