interleukin-8 and Intracranial-Hemorrhages

In patients with acute promyelocytic leukemia (APL), intracranial hemorrhage (ICH), if not identified promptly, could be fatal. It is the leading cause of failure of induction and early death. Thus, biomarkers that could promptly predict severe complications are critical. Here, cytokine differences between patients with APL with and without ICH were investigated to develop predictive models for this complication. The initial cytokine profiling using plasma samples from 39 patients and 18 healthy donors found a series of cytokines that were remarkedly different between patients with APL and healthy controls. The APL patients were subsequently divided into high and low white blood cell count groups. Results showed that tumor necrosis factor a and interleukin 8 (IL-8) were vital in distinguishing patients with APL who did or did not develop ICH. In addition, verification in 81 patients with APL demonstrated that the two cytokines were positively correlated with the cumulative incidence of ICH. Finally, in-vitro and in-vivo experimental evidence were provided to show that IL-8 influenced the migration of APL-derived NB4 cells and impaired the blood-brain barrier in PML/RARα positive blast-transplanted FVB/NJ mice. These assessments may facilitate the early warning of ICH and reduce future mortality levels in APL.

Topics: Animals; Cytokines; Interleukin-8; Intracranial Hemorrhages; Leukemia, Promyelocytic, Acute; Mice; Oncogene Proteins, Fusion; Tretinoin; Tumor Necrosis Factor-alpha

Maternal anti-HPA-1a antibodies can cause severe fetal and neonatal alloimmune thrombocytopenia (FNAIT), complicated by intracranial haemorrhage (ICH). Antenatal treatment with maternal intravenous immunoglobulin (IVIG) seems to protect against ICH even when thrombocytopenia persists. The aim of this study was to investigate if anti-HPA-1a antibodies and IVIG potentially affect vascular endothelial cells (ECs) in order to identify susceptibility for ICH. Human umbilical cord endothelial cells (HUVEC) were incubated with anti-HPA-1a antibodies with or without polyclonal IVIG and evaluated for EC activation. Maternal sera with anti-HPA-1a antibodies affected neither the EC expression of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and tissue factor (TF) nor the release of van Willebrand factor (vWF) or interleukin (IL)-8 nor the integrity of ECs. Maternal sera obtained after IVIG treatment and polyclonal IVIG decrease constitutive and cytokine-induced ICAM-1 and VCAM-1 expression on ECs. The results show that maternal anti-HPA-1a antibodies cause no activation or damage of ECs in this model. The clinical relevance of the de-activating properties of IVIG on EC activation with respect to ICH deserves further investigation.

Topics: Antibodies, Anti-Idiotypic; Antigens, Human Platelet; Endothelial Cells; Female; Fetal Blood; Humans; Immunoglobulins, Intravenous; Infant, Newborn; Integrin beta3; Intercellular Adhesion Molecule-1; Interferon-gamma; Interleukin-8; Intracranial Hemorrhages; Maternal-Fetal Exchange; Pregnancy; Thromboplastin; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; von Willebrand Factor