Cytokine 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 inhibitor, effectively suppressed the cytokine storm, mitigated organ damage, and increased survival rates in mice. The findings present new insights to treat fatal jellyfish stings.