Kinetics of IL-7 and IL-15 Levels after Allogeneic Peripheral Blood Stem Cell Transplantation following Nonmyeloablative Conditioning

Background: We analysed kinetics of IL-7 and IL-15 levels in 70 patients given peripheral blood stem cells after nonmyeloablative conditioning. Methods: EDTA-anticoagulated plasma and serum samples were obtained before conditioning and about once per week after transplantation until day 100. Samples were aliquoted and stored at 280uC within 3 hours after collection until measurement of cytokines. IL-7 and IL-15 levels were measured by ELISAs. Results: Median IL-7 plasma levels remained below 6 pg/L throughout the first 100 days, although IL-7 plasma levels were significantly higher on days 7 (5.1 pg/mL, P = 0.002), 14 (5.2 pg/mL, P,0.001), and 28 (5.1 pg/mL, P = 0.03) (but not thereafter) than before transplantation (median value of 3.8 pg/mL). Median IL-15 serum levels were significantly higher on days 7 (12.5 pg/mL, P,0.001), 14 (10.5 pg/mL, P,0.001), and 28 (6.2 pg/mL, P,0.001) than before transplantation (median value of 2.4 pg/mL). Importantly, IL-7 and IL-15 levels on days 7 or 14 after transplantation did not predict grade II–IV acute GVHD. Conclusions: These data suggest that IL-7 and IL-15 levels remain relatively low after nonmyeloablative transplantation, and that IL-7 and IL-15 levels early after nonmyeloablative transplantation do not predict for acute GVHD

Glucocorticoid Treatment for Bronchopulmonary Dysplasia

Although there is supporting evidence that glucocorticoids improve the short-term pulmonary outcome of newborns, studies indicate significant long-term side effects with neurological sequelae. Corticosteroids can be administered by any route and the licensed products differ significantly in their pharmacological properties and (side) effects. Treatment schedules and dosing regimens vary significantly. Consequently, studies are difficult to compare and to summarise. However, to date, there is no dosing strategy which can always considered to be safe. This provides a dilemma for the treating clinician, who has to balance possible benefits against probable harms in individual patients. This book chapter will first highlight the general mechanism of action of corticosteroids both as natural hormones and as newly synthetised drugs. We will then focus on the function of corticoids during inflammation and their special role in lung development. We will present the clinical data and summarise the current evidence for glucocorticoid treatment strategies ranging from intravenous application to inhalation. Key aspects are the different treatment strategies with dexamethasone and hydrocortisone, because these are the most heavily used substances in newborns. We will take into account different modes of administration, different substances and dosing schedules before ending with some conclusions