HUMAN RECOMBINANT INTERLEUKIN-1-BETA INDUCES THROMBOXANE A(2) RELEASEIN POLYMORPHONUCLEAR LEUKOCYTES, MACROPHAGES AND PLATELETS - EFFECT OF IL-1 RECEPTOR ANTAGONIST

Prostaglandins and thromboxanes (Txs) are produced by polymorphonuclea rs (PMNs) and macrophages (MOs) in response to various stimuli. PMNs w ere separated from other human blood cells and MOs were separated from rat peritoneal lavage. In this paper we show that human recombinant i nterleukin-1 (hrIL-1) can stimulate the release of thromboxane B-2 (Tx B(2)) by PMNs and MOs. In addition, we have shown that aggregation of PMNs may occur when calcium ions (7 mM) and hrIL-1 (100 ng/ml) are add ed 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 treat ment of human platelets with hrIL-1 shows that after 15 min incubation TxB(2) is released. In addition, we compared the aggregation of plate lets 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 plat elets, in this case the aggregation is reversible, In conclusion, hrIL -1 beta stimulates TxB(2) release in PMNs, MOs 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, pret reated 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 mu g/ml, th e release of TxB(2) was partially inhibited. IL-1ra may play a signifi cant role in the control of IL-1 and LPS induction in the release of T xB(2).