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

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 µ/mL HU or zileuton, 2.5 µ/mL concanavalin A (ConA), 20 µ/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 byH-thymidine uptake. Results: While HU reduced lymphocyte proliferation in response to mitogens (