Endotoxin, or LPS tolerance, is an immunomodulatory mechanism that protects the host against secondary LPS exposure and may prevent endotoxic shock. During the development of tolerance, LPS binds to TLR4 and signals the release of cytokines including type I IFN, which has shown to have immunomodulator properties. The role of type I IFN in the induction of LPS tolerance was the topic of interest in a recent publication by Dr. Ali Ashkar’s research group. The study, led by former undergraduate thesis student Yalda Karimi, suggests that type I IFN does not play a role in LPS tolerance in vitro. Examining peritoneal macrophages from both wild type and IFNR KO mice in vitro, they showed that there is comparable, reduced cytokine production after secondary LPS exposure. In addition, both strains of mice received small doses of LPS to induce tolerance, and were then protected from a lethal dose of LPS. The results from this study show that unlike what was expected, type I IFN does not seem to play a role in endotoxin tolerance, and further studies are required to understand the exact mechanisms leading to tolerance. Read the full study here.


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