The regulation of platelet aggregation in vitro by interleukin-1beta and tumor necrosis factor-alpha: changes in pregnancy and in pre-eclampsia.
Platelet activation occurs in early pregnancy in women at risk of developing pre-eclampsia. Cytokines have been implicated in the pathogenesis of pre-eclampsia, so we determined the effects of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) on the in vitro aggregation of human platelets. IL-1beta increased aggregation of platelets from non-pregnant and pre-eclamptic women, and inhibited the aggregation of platelets from normal pregnant women. This latter effect was linked to a diminished P-selectin expression on ADP-stimulated whole blood platelets in normal pregnant women (p = 0.011). Platelet aggregation in response to ADP was found to be inhibited after preincubation with TNF-alpha in non-pregnant (38%, p = 0.01) and in normal pregnant women (54%, p = 0.001) and not affected in pre-eclamptic women. The inhibitory effects of TNF-alpha were mediated through the P75 receptor for TNF-alpha.
Bar
J
J
Department of Obstetrics and Gynaecology, Rabin Medical Centre, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Israel.
Zosmer
A
A
Hod
M
M
Elder
M G
MG
Sullivan
M H
MH
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D019007:P-Selectin / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy / Q000097:blood*; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood*; D011994:Recombinant Proteins / Q000494:pharmacology; D015290:Second Messenger Systems / Q000187:drug effects; D012795:Sialoglycoproteins / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D019007:P-Selectin; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D006152:Cyclic GMP