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 .