Cytokine 77 (2016) 63–71 Contents lists available at ScienceDirect Cytokine journal homepage: www.journals.elsevier.com/cytokine Regulation of inflammatory biomarkers by intravenous methylprednisolone in pediatric ARDS patients: Results from a double-blind, placebo-controlled randomized pilot trial Andreas Schwingshackl a, ⇑ , Dai Kimura b , Cynthia R. Rovnaghi c , Jordy S. Saravia b , Stephania A. Cormier b , Bin Teng d , Alina N. West b , Umberto G. Meduri e , Kanwaljeet J.S. Anand f a Department of Pediatrics, Mattel Children’s Hospital at UCLA, Los Angeles, CA, United States Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States c Pain Neurobiology Laboratory, University of Tennessee Health Science Center, Memphis, TN, United States d Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, United States e Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN, United States f Department of Pediatrics, Stanford University, Stanford, CA, United States b a r t i c l e i n f o Article history: Received 15 May 2015 Received in revised form 13 October 2015 Accepted 19 October 2015 Keywords: ARDS Lung injury Cytokines Chemokines Mediators Pediatrics Steroids Glucocorticoids Inflammation a b s t r a c t Objective: A double-blind, randomized controlled trial showed that low-dose glucocorticoid therapy in pediatric ARDS patients is feasible and may improve both ventilation and oxygenation indices in these patients. However, the molecular mechanisms underlying potential changes in outcomes remain unclear. Based on these clinical findings, this study was designed to examine the effects of intravenous methyl- prednisolone on circulating inflammatory biomarkers in pediatric ARDS patients. Design: Double-blind, placebo-controlled randomized trial with blood collection on study entry and day 7. Setting: Tertiary care children’s hospital. Patients: Children (0–18 years) with ARDS undergoing mechanical ventilation. Interventions: 35 children were randomized within 72 h of mechanical ventilation. The glucocorticoid group received methylprednisolone 2 mg/kg loading dose followed by 1 mg/kg/day continuous infusion from days 1 to 7. Both groups were ventilated following the ARDSnet recommendations. WBC and differen- tial cell counts, plasma cytokines and CRP levels, and coagulation parameters were analyzed on days 0 and 7. Results: At study entry, the placebo group had higher IL-15 and basophil levels. On day 7, in comparison to study entry, the placebo group had lower IL-1 a , IFN- c and IL-10 levels. The glucocorticoid group had lower INF- a , IL-6, IL-10, MCP-1, G-CSF and GM-CSF levels, and higher IL-17 a levels on day 7 in comparison to study entry. Total and differential cell counts remained unchanged within the placebo group between days 0 and 7, whereas in the glucocorticoid group total WBC and platelets counts were increased on day 7. Pearson’s correlation studies within the placebo and glucocorticoid groups revealed positive and negative correlations between cytokine levels, cell counts, coagulation parameters and relevant clinical parameters of disease severity identified in our previous study. Multiple regression models identified several cytokines as predictors for alterations in clinical parameters of disease severity. Conclusion: This pilot study shows the feasibility of simultaneously measuring multiple inflammatory cytokines, cell counts and coagulation parameters in pediatric ARDS patients. We report statistical models that may be useful for future, larger trials to predict ARDS severity and outcomes. O 2015 Elsevier Ltd. All rights reserved. Abbreviations: ARDS, Acute Respiratory Distress Syndrome; GC, glucocorticoid; EGF, epidermal growth factor; FGF-2, fibroblast growth factor-2; Flt3L, fms-like tyrosine kinase 3 ligand; G-CSF, granulocyte-colony stimulating factor; GM-CSF, granulocyte monocyte-colony stimulating factor; GRO, growth related cytokine; INF- a 2, interferon- a 2; IFN- c , interferon- c ; IL-1 a , interleukin1 a ; IL-1b, interleukin-1b; IL-1ra, interleukin-1 receptor antagonist; IL-2, interleukin-2; IL-3, interleukin-3; IL-4, interleukin-4; IL-5, interleukin-5; IL-6, interleukin-6; IL-7, interleukin-7; IL-8, interleukin-8; IL-9, interleukin-9; IL-10, interleukin-10; IL-12(p40), interleukin-12(p40); IL-12(p70), interleukin- 12(p70); IL-13, interleukin-13; IL-15, interleukin-15; IL-17 a , interleukin-17 a ; IP-10, interferon-inducible protein-10; MCP-1, monocyte chemotactic protein-1; MCP-3, monocyte chemotactic protein-3; MDC, macrophage-derived chemokine; MIP-1 a , macrophage inhibitory protein-1 a ; MIP-1b, macrophage inhibitory protein-1b; sCD40L, soluble CD40 ligand; TGF- a , transforming growth factor- a ; TNF- a , tumor necrosis factor- a ; TNF-b, tumor necrosis factor-b; VEGF, vascular endothelial growth factor; WBC, white blood cells; PT, prothrombin time; PTT, partial thromboplastin time; CRP, C-reactive protein; ICU, intensive care unit. ⇑ Corresponding author at: Mattel Children’s Hospital at UCLA, Department of Pediatrics, 10833 Le Conte Ave, 12-494 MDCC, Los Angeles, CA 90095, United States. E-mail address: aschwingshackl@gmail.com (A. Schwingshackl). http://dx.doi.org/10.1016/j.cyto.2015.10.007 1043-4666/O 2015 Elsevier Ltd. All rights reserved.