<?xml version='1.0' encoding='UTF-8'?><xml><records><record><source-app name="HighWire" version="7.x">Drupal-HighWire</source-app><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Kuvibidila, Solo</style></author><author><style face="normal" font="default" size="100%">Warrier, Rajasekharan P.</style></author><author><style face="normal" font="default" size="100%">Haynes, Johnson</style></author><author><style face="normal" font="default" size="100%">Baliga, Surendra B.</style></author></authors><secondary-authors></secondary-authors></contributors><titles><title><style face="normal" font="default" size="100%">Hydroxyurea and Zileuton Differentially Modulate Cell Proliferation and Interleukin-2 Secretion by Murine Spleen Cells: Possible Implication on the Immune Function and Risk of Pain Crisis in Patients with Sickle Cell Disease</style></title><secondary-title><style face="normal" font="default" size="100%">Ochsner Journal</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2015-09-21 00:00:00</style></date></pub-dates></dates><pages><style  face="normal" font="default" size="100%">241-247</style></pages><volume><style face="normal" font="default" size="100%">15</style></volume><issue><style face="normal" font="default" size="100%">3</style></issue><abstract><style  face="normal" font="default" size="100%">Background Hydroxyurea (HU) reduces major complications associated with sickle cell disease in part because of the induction of fetal hemoglobin. However, because of its antiproliferative property, its long-term use may impair immunity. Zileuton, a derivative of HU, also induces fetal hemoglobin and has antiinflammatory properties, a feature that can reduce the risk of sickling. Our goal was to investigate the capacity of both drugs to modulate the secretion of interleukin-2 (IL-2), a regulatory cytokine for immune responses.Methods Spleen cells obtained from 11 4-month-old C57BL/6 female mice were incubated without and with 10 μg/mL HU or zileuton, 2.5 μg/mL concanavalin A (ConA), 20 μg/mL phytohemagglutinin (PHA), and 50 ng/mL anti-CD3 antibody for 12-48 h. IL-2 was measured in the supernatant by enzyme-linked immunosorbent assay and cell proliferation by 3H-thymidine uptake.Results While HU reduced lymphocyte proliferation in response to mitogens (P&lt;0.05), zileuton did not. Baseline IL-2 concentration and PHA-induced IL-2 were not significantly affected by either drug. Contrary to what we expected, while HU increased IL-2 supernatant levels 1.17-fold to 6.5-fold in anti-CD3 antibody–treated cells (P&lt;0.05), zileuton decreased them 35%-65% (P&lt;0.05). Zileuton likely reduced IL-2 levels by inhibiting 5-lipoxygenase, hence leukotriene B4 production, an IL-2 inducer. HU did not decrease IL-2 secretion likely because of its lack of effect on mRNA and protein synthesis.Conclusion Modulation of IL-2 secretion by zileuton and/or reduced lymphocyte proliferation by HU may impair the immune response of patients with sickle cell disease but may also be beneficial by attenuating inflammation independently of fetal hemoglobin induction.</style></abstract></record></records></xml>