Cytokine-induced alteration of platelet and hemostatic function.
A number of nonplatelet-specific cytokines that augment platelet recovery following chemo/radiotherapy have been described. The members of the interleukin 6 (IL-6) family have properties that influence the hematopoietic system beyond their modest thrombocytopoietic effects. Studies performed in a canine model with IL-6 have shown that this factor augments plasma fibrinogen and von Willebrand factor (vWf) concentrations and decreases the level of free protein S. IL-6 appears to decrease the bleeding time in thrombocytopenic dogs, although this effect does not seem to be due to a direct influence of the factor on endothelial vWf or tissue factor production. The factor does not directly alter platelet function in vitro, but when administered to dogs, it increases the sensitivity of the platelets to activation by thrombin. Normal platelets injected into IL-6-treated dogs, and platelets from IL-6-treated dogs injected into normal animals, survive normally. Following injection of either IL-6 or the more specific thrombocytopoietic cytokine thrombopoietin (TPO), IL-6 increases platelet responsiveness to thrombin-induced activation to a greater extent than does TPO. The data show that IL-6 has certain properties that might be construed as prohemostatic, and these properties may prove to be useful clinically.
Burstein
S A
SA
Department of Medicine and the W.K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Peng
J
J
Friese
P
P
Wolf
R F
RF
Harrison
P
P
Downs
T
T
Hamilton
K
K
Comp
P
P
Dale
G L
GL
D000818:Animals; D000911:Antibodies, Monoclonal; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002850:Chromatography, Gel; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011485:Protein Binding; D017293:Protein S / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology; D013921:Thrombocytopenia / Q000188:drug therapy; D013925:Thromboplastin / Q000096:biosynthesis; D013926:Thrombopoietin / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014841:von Willebrand Factor / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D017293:Protein S; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D005340:Fibrinogen; D013926:Thrombopoietin; D013925:Thromboplastin; D013917:Thrombin