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///2013 Abstract Details
2013 Abstract Details2019-08-02T16:57:45-05:00

Noninfectious inflammatory fever causes fetal microglial activation

Abstract Number: BP 2
Abstract Type: Original Research

Scott Segal MD, MHCM1 ; James Marchand PhD2; Zainab Almeer MBBS3; Roman Schumann MD4

Introduction: Up to 1/3 of parturients with epidural analgesia develop clinical fever, compared to those without it, with a relative risk of 3.34.(1) The etiology remains unclear, but appears to be inflammatory but not infectious.(2) Maternal inflammatory fever has been associated with neurologic injury, but animal models have consistently employed intrauterine infection. We developed a noninfectious inflammatory fever model in near-term pregnant rats and examined the effect on the fetal brain.

Methods: Pregnant Sprague Dawley rats received three injections on gestational day 20 (GD20; term=21-22) of IL-6 (1 μg, n=3; or 1, 1.5,and 2.5 μg, IM, n=4) or vehicle (n=4), at 2 h intervals. Core temperature was monitored at 30 min intervals, from 1 h prior to 2 h after the injections. 24 h after the first injection, dams were deeply anesthetized, fetuses delivered by cesarean, and fetal brains (IL-6, n=3; vehicle, n=2) were removed and processed for immunohistochemistry. Sections were processed using antibodies specific to the apoptosis marker, caspase-3, and for activated microglia (aMGlia), ED1. For each brain, sections were processed at three levels of the lateral ventricle (LV): septal (Spt), dorsal hippocampus (DHp) and ventral hippocampus (VHp). Labeled cells surrounding the LV and within the overlying corpus callosum (CC) were counted. Differences in temperature between treatments were compared by repeated measures MANOVA, and labeled cells by t test.

Results: Both IL-6 regimens increased temperature in both constant and escalating dose groups, with no difference between IL-6 groups (p=.75), which were pooled and were significantly higher than vehicle (p=.0192). 24 h after induction of fever, the fetal brains in both Vehicle and IL6 groups showed few caspase-3 labeled apoptotic cells surrounding the LV or within the overlying CC. In contrast, in the IL-6 group aMGlia were densely localized around the LV and within the CC (see Figure). Counts of aMGlia in the IL-6 group were significantly higher compared to the vehicle group, at all three levels of the LV: Spt, P=.028; DHp, P=.052; and VHp, P=.0052.

Discussion: IL-6 produced moderate fever in near-term pregnant rats and resulted in microglial activation in their fetuses. This model may be a useful one for studying epidural analgesia-associated maternal fever and its potential consequences.

1. Cochrane Database Syst Rev 2011, CD0000331.

2. Obstet Gynecol 2011; 117:588.

SOAP 2013