HMGB1 and serum lipopolysaccharide activity: For example, aseptic trauma during surgery causes an increase in endogenous ligands such as high-mobility group box 1 (HMGB1), or circulating lipopolysaccharide (LPS) in patients with endotoxemia, both of which bind to PRRs on circulating cells, such as Toll-like receptors (TLRs), receptor for advanced glycosylation end-products (RAGE), γ-interferon receptor (IFN-γR), and IL-1R, and induce formation of receptor dimers triggering PRRs signaling axis (Poh et al., 2022; Barreto Chang et al., 2023a) (Figure 3).