Effects of Interleukin-17A on the Early Stages of Arterial Thrombosis in Mice

Purpose: Interleukin (IL)-17A has been suggested to play a role in the growth and organization of thrombi We examined whether IL-17A plays a role in the early stages of thrombosis and whether there are sex differences in the effects of IL-17A. Materials and Methods: We performed a blinded, randomized, placebo-controlled study to compare time to thrombotic occlusion and sex differences therein between mice treated with IL-17A and those treated with saline using a ferric chloride-induced model. We also assessed thrombus histology, blood coagulation, and plasma levels of coagulation factors. Results: Time to occlusion values did not differ between the IL-17A group and the control group (94.6 +/- 86.9 sec vs. 121.0 +/- 84.4 sec, p=0.238). However, it was significantly shorter in the IL-17A group of female mice (74.6 +/- 57.2 sec vs. 130.0 +/- 76.2 sec, p=0.032). In rotational thromboelastometry, the IL-17A group exhibited increased maximum dot firmness (71.3 +/- 4.5 mm vs. 66.7 +/- 4.7 mm, p=0.038) and greater amplitude at 30 min (69.7 +/- 5.2 mm vs. 64.5 +/- 5.3 mm, p=0.040) than the control group. In Western blotting, the IL-17A group showed higher levels of coagulation factor XIII (2.2 +/- 1.5 vs. 1.0 +/- 0.9, p=0.008), monocyte chemoattractant protein-1(1.6 +/- 0.6 vs. 1.0 +/- 0.4, p=0.023), and tissue factor (1.5 +/- 0.6 vs. 1.0 +/- 0.5, p=0.003). Conclusion: IL-17A plays a role in the initial st ages of arterial thrombosis in mice. Coagulation factors and monocyte chemoattractant protein-1 may be associated with IL-17A-mediated thrombosis.