Hello,
I am in the process of designing an experiment in which I am hoping to induce a medium-term inflammatory response. I was considering using repeated LPS injections over a week or so, and have also been considering time-release pellets to release a constant amount of LPS into the system daily. I am concerned about the possibility of endotoxin tolerance, but have not found any literature on endotoxin tolerance during LPS exposure, only in a "preconditioning -> gap -> subsequent LPS challenge" type of model.
Is endotoxin tolerance dependent on a gap between challenges? Or is there evidence that it would occur gradually over the course of constant administration of LPS?
Any guidance or links to published reports would be much appreciated. Thank you!
Hi Rebecca, everything we eat and drink has some LPS in it.
In addition more than half of our intestinal cells are bacteria so it is safe to assume that there is some innate tolerance.
Injecting LPS into the circulation is a different thing. A single bolus into humans can cause septic shock and death. A single bolus into mice is less deleterious and is used in my company to induce PAI-1 expression. As far as I know, mice are more resistant to repeated LPS challenges.
Hey, Rebecca. As you have pointed out, the LPS response is highly dependent on the injection paradigm. However, endotoxin tolerance can be induced with repeated injections of escalating dose with no gap period. See PMID: 15885308 as an example of high-dose IP LPS in rats, and PMID: 29643512 for an example of moderate-dose IP LPS in mice.
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