SummaryThe effect of IL-6 on in vitro platelet function was investigated. Platelet-rich plasma (PRP) incubated with IL-6 showed a dose dependent enhancement of agonist induced maximum aggregation (AIMA) and secretion of thromboxane B2 (TXB2) as measured by RIA, in short term incubations. Dazoxiben (0.2 to 160 (µM) pretreated PRP incubated with IL-6 and aggregated with ionophore A23187, showed a dose dependent inhibition of TXB2 secretion concomitant with a dose dependent abrogation of IL-6’s enhancement of AIMA. A similar abrogation of AIMA was observed when these experiments were repeated using indomethacin. Further, PRP incubated with IL-6 showed a dose dependent increase in TXB2 and BTG secretion as measured by RIA and an increased incorporation of actin binding protein, talin, and myosin into the cytoskeletal core (triton insoluble residue) as shown by SDS-PAGE. The integrin glycoprotein Ilia (GPIIIa) was also observed to be retained into the cytoskeleton by immunoblot. These results suggest that IL-6 activates platelets in vitro and enhances AIMA via a mechanism involving arachidonic acid metabolism.
We recently reported that thrombocytopenia and bleeding are often limiting effects of immunotherapy with interleukin-2 (IL-2). In order to understand the mechanisms that lead to this unexpected clinical toxicity, we studied the effects of IL-2 on in vitro platelet function. When platelet aggregation was studied using whole blood (impedance, electrical) aggregometry, inhibition of aggregation was detected within_l_min of the addition of exogenous IL-2 to whole blood. IL-2-induced platelet secretion was quantified by radioimmunoassay (RIA) of PF4, BTG, and TXB 2 independent of the addition of an aggregating agonist (ADP). Platelet secretion and inhibition of aggregation were an indirect consequence of a cellular effect of IL-2 on mononuclear cells, since aggregation was normal when whole blood was depleted of mononuclear cells and its reconstitution with autologous mononuclear cells led to a cell concentration-dependent inhibitory effect of aggregation and release of a-granule components in the presence of IL-2. In order to understand the mechanism of platelet secretion mediated by IL-2-activated mononuclear cells, we quantified the release of eicosanoid products from cultures of mononuclear cells exposed to IL-2 and found a significant increase in TXB 2 . Our results indicate that platelet secretion, indirectly initiated by IL-2-activated cells, is followed by inhibition of aggregation. These findings may not only have important implications for the planning of clinical immunotherapy trials with IL-2, but may also provide a novel link for a better understanding of the relationships between the hemostatic and the immune systems.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.