David P Schrijver, Rutger J Röring, Jeroen Deckers, Anne de Dreu, Yohana C Toner, Geoffrey Prevot, Bram Priem, Jazz Munitz, Eveline G Nugraha, Yuri van Elsas, Anthony Azzun, Tom Anbergen, Laszlo A Groh, Anouk M D Becker, Carlos Pérez-Medina, Roderick S Oosterwijk, Boris Novakovic, Simone J C F M Moorlag, Aron Jansen, Peter Pickkers, Matthijs Kox, Thijs J Beldman, Ewelina Kluza, Mandy M T van Leent, Abraham J P Teunissen, Roy van der Meel, Zahi A Fayad, Leo A B Joosten, Edward A Fisher, Maarten Merkx, Mihai G Netea, Willem J M Mulder
Immunoparalysis is a compensatory and persistent anti-inflammatory response to trauma, sepsis or another serious insult, which increases the risk of opportunistic infections, morbidity and mortality. Here, we show that in cultured primary human monocytes, interleukin-4 (IL4) inhibits acute inflammation, while simultaneously inducing a long-lasting innate immune memory named trained immunity. To take advantage of this paradoxical IL4 feature in vivo, we developed a fusion protein of apolipoprotein A1 (apoA1) and IL4, which integrates into a lipid nanoparticle...
June 8, 2023: Nature Biomedical Engineering