The effects of LPS (doses indicated) on the selected T_a (top panels) and T_b (bottom panels) of sham-lesioned and POA-lesioned rats.

<p>The effects of LPS (doses indicated) on the selected T_a (top panels) and T_b (bottom panels) of sham-lesioned and POA-lesioned rats.</p

Electrolytic ablation of the DMH: histological verification and effects on autonomic thermoregulation.

<div><p>(A) Serial coronal brain sections are shown for a sham-lesioned rat and a DMH-lesioned rat. InfS, infundibular stem.</p> <p>Other abbreviations used are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000001#pone-0000001-g001" target="_blank">Figures 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000001#pone-0000001-g002" target="_blank">[2]</a>.</p> <p>(B) The ability of sham-lesioned and DMH-lesioned rats to defend their T_b by autonomic mechanisms during moderate heat exposure (28°C, 2 h) or mild cold exposure (17°C, 2 h).</p></div

The effects of LPS (doses indicated) on the selected T_a (top panels) and T_b (bottom panels) of sham-lesioned and DMH-lesioned rats.

<p>The effects of LPS (doses indicated) on the selected T_a (top panels) and T_b (bottom panels) of sham-lesioned and DMH-lesioned rats.</p

Electrolytic ablation of the PVH: histological verification and effects on autonomic thermoregulation.

<div><p>(A) Serial coronal brain sections are shown for a sham-lesioned rat and a PVH-lesioned rat. Arc, arcuate hypothalamic nucleus; ME, median eminence; mt, mammillothalamic tract; sox, supraoptic decussation; VMH, ventromedial hypothalamic nucleus.</p> <p>Other abbreviations used are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000001#pone-0000001-g001" target="_blank">Figure 1</a>.</p> <p>(B) The ability of sham-lesioned and PVH-lesioned rats to defend their T_b by autonomic mechanisms during moderate heat exposure (28°C, 2 h) or mild cold exposure (17°C, 2 h).</p></div

Circulating PGE₂ Initiates LPS Fever in Rats: Direct Evidence

<div><p>(A) The effects of i.v. infusion (100 μl/kg/min, 120 min) of the anti-PGE₂ antibody or normal serum 18 h before the experiment (pretreatment) on the T_c and heat loss index responses of rats injected (arrow) with LPS at thermoneutrality (30 °C).</p> <p>(B) The effects of the i.c.v. infusion (2.7 μl/min, 15 min) of the same anti-PGE₂ antibody or normal serum 18 h before the experiment (pretreatment) on the same responses. Note that the i.c.v. infusion was aimed at testing whether minute amounts of the antibody in the brain are sufficient to suppress LPS fever (and not at testing whether fever is altered by neutralization of PGE₂ in the brain).</p> <p>Change in T_c was calculated by subtracting the T_c value at a given point from that at the time of injection (time zero). In (A), the absolute T_cs at time zero were 38.2 ± 0.1 °C and 38.1 ± 0.2 °C for the groups treated with i.v. normal serum and antibody, respectively. In (B), the initial T_cs were 38.4 ± 0.1 °C and 38.2 ± 0.2 °C for the groups treated with i.c.v. normal serum and antibody, respectively.</p> <p>(C) The levels of anti-PGE₂ antibody in the blood plasma and whole brain of rats pretreated with i.v. or i.c.v. antibody. Blood samples and brains were collected immediately after the temperature responses were recorded, i.e., approximately 20 h after pretreatment with the antibody. Antibody levels (means ± SE) are expressed as microgram of neat antibody per gram of either plasma or brain tissue. The detection limit for each assay and the number of rats in each group <i>(n)</i> are indicated. An asterisk (*) indicates a significant difference from the group pretreated with normal serum (<i>p</i> < 0.05; two-way analysis of variance for repeated measures followed by the Tukey test).</p></div

Identification of the Pulmonary and Hepatic Cells Producing PGE₂ at the Onset of LPS Fever in Rats

<p>Immunolocalization of COX-2 in the lung and liver and identification of the cell types expressing this enzyme. Top row: tissue localization of COX-2 (green immunofluorescence) in the lung and liver of rats at 40 min after i.v. injection of saline or at the onset of the first febrile phase (i.e., 40 min after i.v. injection of LPS, 10 μg/kg) at thermoneutrality. Next rows: dual localization of LPS-induced COX-2–immunoreactivity (green; left column) with either the macrophage marker ED2 or the endothelial cell marker RECA1 (red; middle column) in the lung and liver at the onset of the first febrile phase. Doubly labeled cells appear yellow in the merged confocal images (right column). White arrows and black arrowheads mark examples of doubly and singly (COX-2 only) labeled cells, respectively. Scale bars represent 40 μm.</p

Circulating PGE₂ Initiates LPS Fever in Rats: Circumstantial Evidence

<div><p>(A) The effects of i.v. infusion (horizontal bar) of BSA-bound PGE₂ or BSA on T_c and heat loss index of rats kept at a neutral ambient temperature (30 °C).</p> <p>(B) The effects of i.v. bolus injection (arrow) of LPS or saline on the same parameters.</p> <p>Change in T_c was calculated by subtracting the T_c value at a given point from that at the start of infusion or injection (time zero). In (A), the absolute T_cs at time zero were 38.3 ± 0.1 °C, 38.5 ± 0.1 °C, and 38.4 ± 0.2 °C for the groups treated with BSA and with the lower and higher doses of BSA-bound PGE₂, respectively. In (B), initial T_cs were 38.2 ± 0.1 °C and 38.3 ± 0.1 °C for the groups treated with saline and LPS, respectively. The heat loss index was calculated as a quotient of two temperature gradients: skin-ambient and colonic-ambient; this index varies between 0 (maximal vasoconstriction) and 1 (maximal vasodilation) [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040284#pbio-0040284-b033" target="_blank">33</a>].</p> <p>(C) The levels of PGE₂ in the venous and arterial blood of rats 40 min after i.v. injection of LPS or saline at thermoneutrality. This time point corresponds to the maximal thermoeffector activity (minimal heat loss index) to produce the first phase of LPS fever as shown in (B). All doses are indicated. Means ± SE are presented. The number of rats in each group <i>(n)</i> is indicated. An asterisk (*) indicates a significant difference from the BSA- or saline-treated group (<i>p</i> < 0.05; two-way analysis of variance for repeated measures followed by the Tukey test in [A] and [B]; Student <i>t</i>-test in [C]).</p></div