HMGB1 is released by activated monocytes and macrophages or necrotic cells, contributing to diseases such as ALI and chronic obstructive pulmonary disease (COPD).[123] RIP3 induces cytokine production in immune cells.[124] RBC transfusion triggers pulmonary endothelial necrosis, upregulating RAGE, which[125] leads to HMGB1 and RIP3 release, exacerbating lung inflammation.[126] HMGB1 and RIP3 activate the TLR4/NF‐κB/MAPK pathway, thereby promoting inflammation in rat lungs.[15] Moreover, at increased levels, they serve as potential biomarkers for early TRALI diagnosis.[15]. Here, TLR4 is linked to chronic obstructive pulmonary disease.