Abstract Background The immunoinflammatory process has been gaining interest in the field of deep vein thrombosis (DVT) due to its bimodal nature of action in thrombogenesis and resolution. As a pleiotropic cytokine, the role of interleukin-6 (IL-6) in DVT remains controversial between being the trigger or messenger in the course of DVT pathology. Purpose To elucidate the role of IL-6 in the pathophysiology of acute DVT. Methods We ligated the femoral vein and performed FITC-filtered light-irradiation on the saphenous vein of 8–12-week-old male C57BL/6J mice a day following intraperitoneal injection of recombinant IL-6 (rIL-6; 0.3 µg/mouse) or phosphate-buffered saline (PBS). Serial in vivo epifluorescence microscopy was employed to assess DVT resolution in relation to the inflammatory cell dynamics. Two-photon microscopy evaluated the pattern of leukocyte migration into the DVT. Furthermore, we generated inferior vena cava (IVC) thrombus by complete ligation in mice receiving continuous rIL-6 (1.2 µg/day) or PBS to evaluate its pathobiological profile at day 2 or 4 through histological staining, quantitative polymerase chain reactions (qPCR), and ex vivo imaging of intrathrombi matrix metalloproteinase (MMP) activity. Results IL-6-treated mice showed accelerated distal-edge DVT resolution that correlated with the intensity of rhodamine 6G-labeled leukocyte-platelet signal at the distal edge of saphenous DVT (Fig. A). While both groups of mice showed comparable stasis blood flow velocity, leukocytes in IL-6-treated mice infiltrated the distal edge of DVT with faster speed and longer migration distance on the Y-axis than in PBS-treated mice (Fig. B). Moreover, IVC thrombus burden was substantially lessened in IL-6-treated mice (Fig. C). Neutrophils and platelets accumulated more prominently, along with more fibrin-collagen deposition instead of erythrocytes, at the distal edge of DVT in IL-6-treated mice, consistent with the in vivo imaging findings. Intrathrombi transcriptomic profiles of this area demonstrated elevated proinflammatory cytokines and chemokines, activation of leukocytes and platelets, and remodelling of the thrombi extracellular matrix, suggesting IL-6-induced local inflammation. However, MMP activity was comparably similar in both groups (Fig. D). Conclusions Our results showed the beneficial role of IL-6 in acute DVT by accelerating thrombus resolution through the confined distal edge’s leukocyte-platelet recruitment and interactions. IL-6 could be promising for promoting "good" inflammation in acute DVT.
Achyar et al. (Sat,) studied this question.