Inhibition of allergic responses by CD40 gene silencing.

BACKGROUND: Gene silencing using small interfering RNA (siRNA) is a potent method of specifically knocking down molecular targets. Small interfering RNA is therapeutically promising, however, treatment of allergic diseases with siRNA has not been explored in vivo. The aim of this study was to evaluate therapeutic effects of CD40 siRNA on inhibition of allergic responses. METHODS: Mice sensitized with ovalbumin (OVA) and alum were treated with CD40 siRNA, scrambled siRNA, or phosphate buffer saline (PBS) alone, and then challenged intranasally with OVA. RESULTS: A significant reduction in nasal allergic symptoms was observed in the CD40 siRNA treated OVA-allergic mice compared to the controls of scrambled siRNA and PBS alone, which is correlated with the decrease of local eosinophil accumulation. CD40 siRNA treatment knocked down CD40 expression on dendritic cells (DCs) in vivo and impaired their antigen presenting function. Treatment with CD40 siRNA resulted in inhibition of OVA-specific T cell response and decrease of interleukin-4 (IL-4), IL-5, and interferon-gamma production from T cells stimulated with OVA. Administration of CD40 siRNA also suppressed CD40 expression on B cells, resulting in down-regulation of OVA-specific immunoglobulin E (IgE), IgG1, and IgG2a levels. Additionally, increased regulatory T cells were observed in the CD40 siRNA treated mice. CONCLUSIONS: The present study demonstrates a novel therapeutic use for siRNA in allergy. CD40 siRNA attenuated allergy through inhibition of DC and B cell functions and generation of regulatory T (Treg) cells.

Chorionic villous haemorrhage is associated with retroplacental haemorrhage.

OBJECTIVE: To examine the frequency of occurrence of chorionic villous haemorrhage in placentas with retroplacental haemorrhage, and to discuss the pathogenesis of these conditions. DESIGN: A retrospective study using histological sections of formalin-fixed, paraffin-embedded placental tissue stained with haematoxylin and eosin. SETTING: Department of Histopathology, Rotunda Hospital, Dublin. SUBJECTS: Sixty cases of retroplacental haemorrhage, 34 cases of chorioamnionitis, and 24 histologically normal placentas. MAIN OUTCOME MEASUREMENT: Presence or absence of chorionic villous haemorrhage. RESULTS: Chorionic villous haemorrhage was present in 31 of 60 cases of retroplacental haemorrhage (51%), one of 34 cases of chorioamnionitis (2.9%) and in no normal placentas. CONCLUSIONS: It is postulated that chorionic villous haemorrhage reflects a disturbance of fetal vascular dynamics and precedes retroplacental haemorrhage. Such a disturbance could trigger the events leading to abruption.