Bleeding induced interleukin-6 decreases blood loss via activation of coagulation

Hemorrhage is known to induce the production of inflammatory cytokines such as interleukin-6 (IL-6), IL-6 plays an intermediate role as a factor in th e activation of coagulation cascade and exerts a lethal effect in sepsis. T o examine the effect of endogenous IL-6 on blood loss, we performed four ex periments in female ddY mice. Enzyme immunoassay using an uncontrolled hemo rrhage model, i.e., 75% tail resection, revealed the production of serum IL -6 (Experiment 1). We also measured cumulative blood loss and survival rate (Experiment 2); measured blood pressure and performed thrombelastogram (TE G) (Experiment 3); and measured plasma thrombin-antithrombin III (TAT) comp lex levels in two groups, one pretreated with 1 mg of anti-IL-6 monoclonal antibody (mAb), and one with normal rat globulin (NRG) using the same model (Experiment 4). The mAb group showed a significantly higher blood loss tha n the NRG group. All mice survived for 5 days in both groups. Blood pressur e did not differ between either group. The TEG results suggest that adminis tration of anti-IL-6 mAb caused mild suppression of coagulation activation, but did not affect fibrinolysis or platelets. In the mAb group, plasma TAT complex concentrations showed a significant decrease compared with the NRG group. In conclusion, hemorrhage-induced IL-6 may contribute to hemostasis through activation of coagulation, thus reducing blood loss.