What will it take to treat patients so that their innate immune systems act like mice & monkeys? Avoid harmful inflammation without being susceptible to infection - a new approach for diseases like #Sepsis & #ARDS. Maybe even chronic inflammatory diseases like #Lupus.

doi.org/10.1186/s100...
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The biggest differences were in genes that weren't LPS responsive themselves, but encoded mediators of inflammation, like #TLR pathway proteins.

It will be important to understand how these differences contribute to susceptibility to systemic to inflammation.

6/

Most surprisingly, we could distinguish sensitive from resilient species even without LPS challenge. Baseline gene expression in sensitive animals had a more inflammatory profile.

6/

We didn't find many differences in the #Proteome or #Lipidome than correlated with sensitivity to inflammation.

But #Leukocytes from resilient and sensitive showed clear differences in their responses, including in genes linked to LPS metabolism.

5/

We did a side-by-side comparison of white blood cell gene expression and plasma proteins and lipids in 10 mammals with different reported susceptibility to lethal inflammation. We measured gene expression in naive leukocytes and following ex vivo stimulate with #LPS.

4/

But wait - mice have robust #InnateImmunity. They eliminate bacteria and viruses well and aren't especially prone to cancer; they just don't suffer the bad effects of systemic inflammation.

Whst causes the difference? Can we learn from it to improve treatments for infection and inflammation?

3/

"Mice lie and monkeys don't always tell the truth."

Despite what in vitro experiments predict, different animals have hugely different susceptibility to harmful, systemic inflammation. It takes 100s- or 1000s-fold more bacterial product to cause lethal inflammation in a mouse than in a human.

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Hi Rod, please include me if you are making a 5th pack. Thanks!