**7. Lipopolysaccharide injection: A model of Endotoxemia**

Probably the most extensively studied animal model of sepsis is based on the intraperitoneal injection of lipopolysaccharide (LPS) [43, 44]. LPS is the major outer surface membrane component present in almost all Gram-negative bacteria and act as extremely strong stimulators of innate [45]. Although this model is simple to learn and perform, it has inherent limitations. The primary ones being that it neglects the direct host-pathogen interactions and is limited to Gram negative organism-induced sepsis. A bolus administration of LPS is essentially a model of severe inflammatory response syndrome (SIRS), rather than a true septic mimetic [46] and there is no microbial source for ongoing LPS, or pathogen associated pattern (PAMP) release. Key to the optimal success of this septic AKI model is amongst others, the use of the proper serology of LPS (E Coli. O111.B4), age of mice [43] and fluid resuscitation [47]. Compared to true human sepsis, endotoxemia results in a rapid and exponential spike in plasma inflammatory cytokines, and this SIRS like condition resolves rapidly [48–50]. This model is of scientific utility in interrogating specific biological mechanisms and pathways, such as the immune response to prototypical stimuli of specific toll-like receptor (TLR) pathways, TLR4.
