Decubitus ulcers are serious problems in elderly long-term bedridden patients. Currently, there are no evidence-based treatment in the early phase decubitus to prevent the development of skin ulcers, except for reducing body weight load, by changing position or using cushions. Ischemia-reperfusion (I/R) injury is characterized by the reperfusion of blood to previously ischemic tissue, which induces cellular injury. I/R injury is associated with vascular infarction or vasospasm in various organs such as the brain, heart, liver, and kidneys, and there is also increasing evidence that cutaneous I/R injury is also associated with the development of decubitus. Interleukin-33 (IL-33) is a member of IL-1 cytokine family that enhance Th2 immune reaction. IL-33 is one of danger signals to elicit inflammation upon tissue damage. We speculated that abundant IL-33 would be released in decubitus ulcer formation (I/R injury), thus we sought to determine if IL-33 acted an important role in the decubitus ulcer formation following I/R and investigate the mechanism. Ulcer area was reduced in IL-33KO mice and sST2 Tg mice compared to WT mice. Anti-IL-33 or anti-ST2L neutralizing antibody reduced the I/R-induced ulceration in WT mice. The number of infiltrating M2 macrophages was larger in IL-33KO mice at day8 I/R ulceration but that of mast cells and neutrophils was less. Real time (RT)-PCR results showed that expression of IL-1β was suppressed, but that of CCL17, related to M2 macrophage differentiation, was upregulated in IL-33KO mice compared to WT mice. In vitro study showed that macrophages from IL-33KO mice was able to produce IL-1β with IL-33 stimulation. These results indicate that blocking of IL-33 signaling would prevent or reduce the decubitus ulcer formation, by reducing mast cells and neutrophil infiltration and increasing M2 macrophage infiltration. We propose that blocking of IL-33 signal would have a great potential in prevention and treatment of early phase decubitus ulcer, which would tremendously contribute to clinical medicine.

ESDR347 - IL-33 deficiency protects skin from ulcer formation in ischemia-reperfusion-induced decubitus mouse model.

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING