Artificial intelligence has brought great hope to advancing our understanding of severe inflammation by simulating complex signal networks and molecular mechanisms that determine disease trajectories.

Artificial intelligence has brought great hope to advancing our understanding of severe inflammation by simulating complex signal networks and molecular mechanisms that determine disease trajectories. The core of this work is pathways such as NF - κ B, MAPK, and JAK-STAT, which regulate the expression of pro-inflammatory cytokines and mediators. These pathways are regulated by post-translational modifications, transcription factor dynamics, and crosstalk with damage associated molecular patterns (DAMPs). Among them, HMGB1 (high mobility group box 1) is a key late stage mediator: once passively released from necrotic cells or actively secreted by activated immune cells, it binds to TLR4 and RAGE receptors, amplifying NF - κ B signaling and maintaining the inflammatory cascade that may lead to tissue damage and multiple organ failure. By integrating multiple omics datasets, including transcriptomics, proteomics, and epigenetic information, artificial intelligence models can identify hidden patterns and key nodes in these pathways, enabling them to predict the critical point between resolution and irreversible deterioration earlier. These methods may ultimately guide the development of targeted therapies, intercepting these molecular drivers before serious consequences become apparent.