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 the activation of coagulation cascade and exerts a lethal effect in sepsis. To examine the effect of endogenous IL-6 on blood loss, we performed four experiments in female ddY mice. Enzyme immunoassay using an uncontrolled hemorrhage 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 (TEG) (Experiment 3); and measured plasma thrombin-antithrombin III (TAT) complex 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 than the NRG group. All mice survived for 5 days in both groups. Blood pressure did not differ between either group. The TEG results suggest that administration 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.
Department of Anesthesiology, Hokkaido University School of Medicine, Sapporo, Japan.
I
I
Katsuyama
T
T
Mayumi
M
M
Kohanawa
Y
Y
Ohta
T
T
Minagawa
O
O
Kemmotsu
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000990:Antithrombin III / Q000032:analysis; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure; D005260:Female; D005342:Fibrinolysis; D005916:Globulins / Q000494:pharmacology; D006470:Hemorrhage / Q000188:drug therapy / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D010447:Peptide Hydrolases / Q000032:analysis; D010976:Platelet Count; D051381:Rats; D015996:Survival Rate; D013916:Thrombelastography
D000911:Antibodies, Monoclonal; D005916:Globulins; D015850:Interleukin-6; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases