Pre-treatment with ibrutinib prior to zymosan challenge reduces myeloid cell recruitment to the peritoneum.
Zymosan induced peritonitis (using 100 ug of zymosan) is a model of acute inflammation characterised by the recruitment of myeloid cells to the peritoneum following injection of zymosan, that is largely resolved after 48-96 h (Regan-Komito et al., 2017). To test if pharmacological inhibition of BTK with the FDA/EMA approved BTK inhibitor ibrutinib would reduce myeloid cell recruitment during acute inflammation C57BL/6 mice were pre-treated with ibrutinib (0.1 - 10 mg/kg; p.o.) 1 h prior to zymosan (100 ug; i.p.). Total peritoneal exudate cells were harvested 16h later and analysed using multicolour flow-cytometry. Total cellularity within the peritoneum increased significantly within 16 h of zymosan challenge (data not shown) and this mainly comprised of neutrophils (CD11b+Ly6C+Ly6G+) (Figure 1A/C), monocytes (CD11b+Ly6C+Ly6G-) (Figure 1A/D). As there is a resident population of B-cells in the peritoneum we also assessed B-cell number (Figure 1B). Ibrutinib treatment decreased total cellularity (Figure 1C), and significantly decreased neutrophil recruitment (Figure 1D) and monocytes recruitment (Figure 1E) into the peritoneum at 16 h, at all doses given compared to mice given vehicle prior to zymosan challenge. Importantly, ibrutinib treatment did not alter B-cells numbers within the peritoneum (Figure 1F). This result demonstrates for a direct role for BTK in myeloid cell recruitment in vivo .