Barbu EA, et al. - Given that sickle cell disease (SCD) is characterized by recurring episodes of acute pain, also referred to as vaso-occlusive crises (VOC), and hydroxyurea (HU) is licensed by the FDA for decreasing frequency of VOCs in SCD; contributors to its clinical effectiveness are raised fetal hemoglobin combined with decrease in the neutrophil count and circulating inflammatory markers. Researchers undertook this study in HbSS patients (in steady-state and VOC), from whom paired plasma samples were obtained. They found that the SCD environment continued to be highly inflammatory and especially at VOC, triggered neutrophil activity, despite HU treatment. In the VOC plasma vs steady state plasma, they detected significantly increased levels of IL-6 and IL-1α, IL-1ra/IL1F3 and adhesion molecule P-selectin. They also found that the levels of IL-6 and IL-1ra were higher in the crises samples that yielded an increased NETs (neutrophil extracellular traps) response, indicating a link of increased NETs generation with increased levels of the inflammatory products of the IL-6 family and regulators of IL-1 family of cytokines during sickle VOCs.