Fig. 1

Gut-lymph hypothesis of gut-origin sepsis and functions of lipocalin (Lcn) 2. Various deleterious stimuli can induce intestinal barrier injury and microbial dysbiosis. The invasion by translocated enteric bacteria or their PAMPs and gut-derived DAMPs sets off a local inflammatory response by immune cells stored in GALT, further impairing the intestinal barrier (first vicious circle). Mesenteric lymphatics transport DAMPs to the systemic circulation where their recognition by immune cells triggers the development of SIRS and MODS (second vicious circle). Here, the therapeutic potential of Lcn2 is considered. Inside the gut, Lcn2 is suggested to maintain intestinal microbiota homeostasis (a) and protect the intestinal barrier against oxidative stress (b). When systemic hyper-inflammation occurs, Lcn2 bolsters its termination (c) and shield organs from MODS (d). GALT gut-associated lymphoid tissue, DAMPs danger-associated molecular patterns, PAMPs pathogen-associated molecular patterns, PRR pattern recognition receptor, SIRS systemic inflammatory response syndrome, MODS multiple organ dysfunction syndrome