Bacterial sepsis causes upregulation of CIRP which binds to TLR4. CIRP-TLR4 interaction in neutrophils leads to upregulation of ICAM-1 expression through NF-κB pathway. Functionally, the ICAM-1+ neutrophils produce excessive iNOS and NETs and promote inflammation and injury to the tissues. CIRP, cold-inducible RNA-binding protein; TLR4, Toll-like receptor 4; NETs, neutrophil extracellular traps; iNOS, inducible nitric oxide synthase; ICAM-1, intercellular adhesion molecule-1; MPO, myeloperoxidase.