Background: Certain human cardiovascular diseases are subject to gender bias with more prevalence in men. Sexual dimorphisms in murine leukocyte responses during inflammation have previously been described, with males recruiting more neutrophils¹. This study aimed to determine sex-differences in storage, trafficking and responses of classical monocytes (CMs), in an acute inflammatory model.

Materials and methods:Peritonitis was induced by intraperitoneal administration of zymosan (1mg) to CX₃CR1^+/gfp mice. Leukocytes were isolated from blood, peritoneal cavity, bone marrow (BM) and spleen. CMs were identified as CX₃CR1⁺Gr1⁺ by flow cytometry.

Results:Equal basal circulating, peritoneal and BM CM numbers were observed between the sexes, however males exhibited a greater splenic storage pool. Expression of key chemokine receptors was similar on splenic CMs from both sexes, as was the basal splenic chemokine environment. In response to zymosan, male mice demonstrated 2-fold greater classical monocytosis at 3h post-administration than females, which translated into greater recruitment to the peritoneum. Reduction in BM cells at 3h indicated mobilization; this was equal in both sexes. Equivalent spleen CM numbers at 3h suggest greater outward flux in males than females. Female resident peritoneal macrophages were more numerous however expression of zymosan-sensing TLR2-TLR6 was equal to males and no sex-differences were seen in the basal or inflamed peritoneal cytokine environments.

Conclusions:These data indicate that male mice have greater splenic stores of CMs and furthermore recruit more CMs to the tissue during peritonitis. Sex-differences in classical monocyte trafficking during inflammation may translate to monocyte/macrophage-dependant pathologies more prevalent in males, like atherosclerosis, and may provide a more personalised method of targeting such diseases.