Human recombinant interleukin-1 beta induces thromboxane A2 release in polymorphonuclear leukocytes, macrophages and platelets: effect of IL-1 receptor antagonist.

Prostaglandins and thromboxanes (Txs) are produced by polymorphonuclears (PMNs) and macrophages (Mphis) in response to various stimuli. PMNs were separated from other human blood cells and Mphis were separated from rat peritoneal lavage. In this paper we show that human recombinant interleukin-1 (hrIL-1) can stimulate the release of thromboxane B2 (TxB2) by PMNs and Mphis. In addition, we have shown that aggregation of PMNs may occur when calcium ions (7 mM) and hrIL-1 (100 ng/ml) are added to the cell preparation, but not when Ca2+ alone, hrIL-1 alone, or first hrIL-1 then calcium are added to the cell preparation. The treatment of human platelets with hrIL-1 shows that after 15 min incubation TxB2 is released. In addition, we compared the aggregation of platelets caused by ADP with that caused by hrIL-1. Human recombinant IL-1 at a concentration of 100 ng/ml also causes little aggregation of platelets, in this case the aggregation is reversible. In conclusion, hrIL-1 beta stimulates TxB2 release in PMNs, Mphis and platelets and this effect increases with addition of Ca2+ ions. The mixture of hrIL-1 and Ca2+ causes little aggregation of PMNs. In monocyte suspensions, pretreated with human recombinant IL-1 receptor antagonist (IL-1ra) 500 ng/ml for 10 min and then treated with LPS or hrIL-1 beta 10 micrograms/ml, the release of TxB2 was partially inhibited. IL-1ra may play a significant role in the control of IL-1 and LPS induction in the release of TxB2.