Figure 4.

Arachidonic acid signaling modulates Ang1/Ang2 ratio and is relevant in murine and human neonatal sepsis. (A) Overall survival of CS-challenged mice with or without prophylactic AA treatment 4–6 h prior to challenge (n = 16 CS, 29 AA mice, derived from two independent experiments; p = 0.003, log rank). (B) ROS (O₂⁻) accumulation in the liver of CS-challenged mice 8 h post challenge as determined by relative fluorescence intensity of dihydroethidium normalized to untreated controls (p < 0.001, paired Wilcoxon rank-sum test, n = 22 controls, 19 cs, and 10 AA treated mice (CS + AA) derived from 3 independent experiments). (C) Serum Ang1 and Ang2 levels in control, challenged (CS) and challenged / AA treated mice (CS + AA) (paired Wilcoxon rank-sum; n = 5 control, 10 cs, and 10 AA treated mice (CS + AA) derived from 3 independent experiments). (D) qPCR analysis of fold changes between ALOX15 (left), PTGS2 (middle) or CYP2J2 (right) to reference gene TUBB in a cohort of septic neonates from Malawi (n = 14 cases and 16 controls; Wilcoxon rank-sum). (E) Plasma sPLA-2 levels in human infants with any LOS vs. no LOS, as measured by ELISA (Wilcoxon rank-sum). (F) Spearman correlation showing relationship between plasma sPLA-2 levels and plasma ANG1 levels (left-panel), plasma ANG2 levels (middle panel) and plasma ANG1/ANG2 ratio (right panel) for all neonates (22 cases and 40 controls) within our cohort (Spearman correlation). Boxplots indicate medians with first and third quartiles (25–75%) indicated by the lower and upper bounds of the box; whiskers extend no further than 1.5 × interquartile range from the hinge. Violin plots display a kernel density curve overlaying a boxplot.