Abstract
Sickness behavior, characterized by on overall reduction in behavioral activity, is commonly observed after bacterial infection. Sickness behavior can also be induced by the peripheral administration of Gram-negative bacterial lipopolysaccharide (LPS) or interleukin-1beta (IL-1β), a pro-inflammatory cytokine released by LPS-activated macrophages. In addition to the microglia, the brain contains perivascular macrophages, which express the IL-1 type 1 receptor (IL-1R1). In the present study, we assessed the role of brain perivascular macrophages in mediating IL-1β-induced sickness behavior in rats. To do so, we used intracerebroventricular (icv) administration of an IL-1β-saporin conjugate, known to eliminate IL-R1-expressing brain cells, prior to systemic or central IL-1β injection. Icv IL-1β-saporin administration resulted in a reduction in brain perivascular macrophages, without altering subsequent icv or ip IL-1β-induced reductions in food intake, locomotor activity, and social interactions. In conclusion, the present work shows that icv IL-1β-saporin administration is an efficient way to target brain perivascular macrophages, and to determine whether these cells are involved in IL-1β-induced sickness behavior.
Highlights
A one-way ANOVA on food intake after ip injection showed that 60 μg/kg of mouse (m)IL-1β-Alexa-488 significantly reduced cumulated food intake 2, 3.5 and 5 h later, as compared to the administration of a vehicle (F(1,14) = 5.94, p < 0.05; F(1,12) = 8.22, p < 0.05; F(1,10) = 5.92, p < 0.05, respectively), indicating that the conjugation reaction did not affect IL-1β’s bioactivity
The aim of the present experiments was to determine the role of IL-1R1-expressing brain perivascular macrophages in mediating IL-1β-induced sickness behavior, using an IL-1R1-saponin conjugate to eliminate cells containing IL-1R1 [15]
The administration of this conjugate reduced the number of CD163-positive brain perivascular macrophages, known to express IL-1R1 [18], without altering the immunoreactivity for endothelial cells or astrocytes, but did not affect sickness behavior in response to either icv or ip administration of IL-1β
Summary
Sickness behavior, consisting of reductions in food intake (hypophagia), locomotor activity, and social interactions, is commonly associated with bacterial infection [1,2,3]. Proinflammatory cytokines, such as interleukin-1 (IL-1), produced by activated immune cells in response to bacterial lipopolysaccharides (LPS) [4,5,6], reduce food intake, activity, and social interactions, and mediate sickness behavior [7,8,9,10,11,12].
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