Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults.
Catecholamine-containing projections from the medulla have been implicated in the mediation of activational responses of the paraventricular nucleus of the hypothalamus (PVH) provoked by moderate doses of interleukin-1 (IL-1). To test the generality of this mechanism, rats bearing unilateral transections of aminergic projections were challenged with intravenous IL-1 (2 microg/kg), bacterial lipopolysaccharide (LPS; 0.1, 2.0, or 100 microg/kg), or saline and perfused 3 hours later; their brains were then prepared for quantitative analysis of Fos induction and relative levels of corticotropin-releasing factor (CRF) mRNA. LPS provoked a robust and dose-related increase in Fos expression within the PVH on the intact side of the brain at all doses tested; the response to IL-1 approximated that to the lowest LPS dose. On the lesioned side, Fos induction was significantly reduced at all dosage levels but was eliminated only at the lowest dosage. The percentage reduction was greatest (75%) in IL-1-challenged rats and was progressively less in animals treated with increasing LPS doses (67, 59, and 46%, respectively). Specificity of aminergic involvement was tested by using intra-PVH administration of the axonally transported catecholamine immunotoxin, antiDBH-saporin. This treatment abolished IL-1-induced elevations of Fos-ir and CRF mRNA in the PVH but left intact comparable responses to restraint stress. These data support a specific involvement of ascending catecholaminergic projections in mediating PVH responses to IL-1 and LPS. Residual Fos induction seen in lesioned animals in response to higher doses of LPS provides a basis for probing additional circuits that may be recruited in a hierarchical manner in response to more strenuous or complex immune insults.
Schiltz
Jennifer C
JC
Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies and Foundation for Medical Research, La Jolla, California 92037, USA.
Sawchenko
Paul E
PE
D000344:Afferent Pathways / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D001933:Brain Stem / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000276:immunology; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects*; D000922:Immunotoxins / Q000633:toxicity; D017403:In Situ Hybridization; D053583:Interleukin-1beta / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000293:injuries / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000379:methods
D000911:Antibodies, Monoclonal; D002395:Catecholamines; D000922:Immunotoxins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016761:Oncogene Proteins v-fos; D003346:Corticotropin-Releasing Hormone; D004299:Dopamine beta-Hydroxylase