Elsevier

Neuroscience

Volume 137, Issue 2, 2006, Pages 717-726
Neuroscience

Research paper
Systems neuroscience
Peripheral injection of lipopolysaccharide prevents brain recruitment of leukocytes induced by central injection of interleukin-1

https://doi.org/10.1016/j.neuroscience.2005.08.087Get rights and content

Abstract

I.c.v. injection of interleukin-1β induces infiltration of leukocytes into the brain. I.p. injection of bacterial endotoxin lipopolysaccharide induces the expression of interleukin-1 in the CNS without causing the entry of leukocytes into the brain. This suggests that during systemic inflammation trafficking of potentially damaging leukocytes into the CNS is inhibited. In this study, we investigated the effects of peripheral injection of lipopolysaccharide on brain leukocyte recruitment induced by i.c.v.-interleukin-1 in mice. I.c.v.-interleukin-1 induced widespread infiltration of leukocytes into the brain 16 h after the injection. Pretreatment with i.p.-lipopolysaccharide 2 h before the i.c.v. interleukin-1 injection completely blocked interleukin-1-induced leukocyte infiltration, whereas i.p.-LPS only attenuated the effect of interleukin-1 if it was given 12 h before i.c.v. interleukin-1 injection. I.p.-lipopolysaccharide given 24 h before i.c.v. interleukin-1 injection did not alter interleukin-1 induced leukocyte infiltration. I.c.v.-interleukin-1 induced expression of p- and e-selectins in brain vasculatures prior to the appearance of leukocytes in the brain parenchyma. Induction of p- and e-selectin was inhibited by the pretreatment of i.p.-lipopolysaccharide 2 h, but not 24 h, before i.c.v.-interleukin-1 injection. I.c.v.-interleukin-1-induced leukocyte infiltration was diminished in both e- and p- selectin knockout animals. These results suggest that systemic inflammation actively inhibits recruitment of leukocytes by CNS. Inhibition of the expression of p- and e-selectins is a mechanism by which peripheral inflammation regulate CNS leukocyte recruitment.

Section snippets

Animals and i.c.v. IL-1β injection

Control male mice (C57BL/6) and p- and e-selectin knockout mice, weighing 20–30g at the age of 6–10 weeks, were purchased from the Jackson Laboratory (Bar Harbor, ME, USA). Mice were used one week after acclimation to the animal facility. For i.c.v. injection, all mice were anesthetized by i.p. injection of 2 mg/20g Nembutal (Abbott Laboratories, North Chicago, IL, USA) and then securely fixed on the small animal stereotaxic (David Kopf Instrument, Tujunga, CA, USA). After surgically opening a

Results

No leukocytes (CD45+) cells were found in i.c.v.-saline-injected brain (Fig. 1A). I.c.v. injection of IL-1β (20 ng/mouse) induced adherence and subsequent infiltration of leukocytes (CD45+ cells) in the brain at 8 and 16 h post-injection, respectively (Fig. 1B and 1C). Inset in Fig. 1B (a high-magnification photograph taken from 1B section) shows that the appearance of blood vessel-like staining in Fig. 1B was due to CD45+ cells adhering to the blood vessels. On the contrary, i.p.-LPS (1mg/kg)

Discussion

The inflammatory cytokine IL-1 plays a unique role in the communication between the immune system and the CNS. It is well known that CNS responses induced by systemic inflammation such as fever, increased slow-wave sleep, and sickness behavior are, at least in part, mediated by the action of IL-1 in the CNS (Quan and Herkenham, 2002). The neural effects of IL-1 were further substantiated by the profound actions of IL-1 in altering neurotransmitter metabolism (Dunn et al., 1999), neuropeptide

Acknowledgment

This study was supported by grants from the National Institutes of Health (R01 NS40098) and (R01 AI059089) to N.Q.

References (32)

  • N. Quan et al.

    Induction of interleukin-1 in various brain regions after peripheral and central injections of lipopolysaccharide

    J Neuroimmunol

    (1994)
  • N. Quan et al.

    Time course and localization patterns of interleukin-1β messenger RNA expression in brain and pituitary after peripheral administration of lipopolysaccharide

    Neuroscience

    (1998)
  • G.H. Allcock et al.

    Neutrophil accumulation induced by bacterial lipopolysaccharideeffects of dexamethasone and annexin 1

    Clin Exp Immunol

    (2001)
  • D.C. Anthony et al.

    Age-related effects of interleukin-1 beta on polymorphonuclear neutrophil-dependent increases in blood-brain barrier permeability in rats

    Brain

    (1997)
  • A. Basu et al.

    Interleukin-1a master regulator of neuroinflammation

    J Neurosci Res

    (2004)
  • M. Bernardes-Silva et al.

    Recruitment of neutrophils across the blood-brain barrierthe role of E- and P-selectins

    J Cereb Blood Flow Metab

    (2001)
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