Ibrutinib treatment 1 h prior to zymosan challenge reduces myeloid cell recruitment over a 48 h time course.
Having shown that ibrutinib treatment reduced both neutrophil and monocyte recruitment at 16h, we wanted to understand the full kinetics of myeloid cell recruitment over a 48 h time period. Mice were given ibrutinib (10 mg/kg; p.o.) 1 h prior to zymosan challenge and total peritoneal exudate cells harvested at 2, 4, 16 and 48 h. Following zymosan challenge there is rapid recruitment of cells into the peritoneum within the first 4 h (Figure 2A), of which the majority are Ly6C+Ly6G+ neutrophils (Figure 2B), this is followed by the peak infiltration of Ly6C+Ly6G- monocytes at 16 h (Figure 2C). Ibrutinib treatment 1 h prior to zymosan challenge significantly reduced peak neutrophil recruitment at 2 and 4 h (Figure 2D/E). The initial peritoneal monocyte recruitment from the blood monocytes (2 and 4 h) was unaltered in ibrutinib treated mice (Figure 2H and I) but BTK inhibition significantly reduced the peak monocyte recruitment at 16 h and was maintained up to 48 h (Figure J and K). Overall, the magnitude of cellular recruitment is significantly reduced in mice given a single ibrutinib treatment prior to zymosan challenge compared to mice given vehicle prior to zymosan challenge over the entire 48 h time frame studied (Figure 2 L-M).