Chemical destruction of brain noradrenergic neurons affects splenic cytokine production.
The neurotransmitter noradrenaline (NA) plays a pivotal role in immune regulation. Here we used the selective neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to investigate the impact of central NA depletion on cytokine production by splenic monocytes/macrophages and T cells. Intraperitoneal administration of DSP-4 in adult rats induced a substantial reduction of noradrenergic neurons in the locus coeruleus and the A5 cell group. The degeneration of brainstem noradrenergic neurons was accompanied by a significant decrease in the production of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha by lipopolysaccharide-stimulated splenocytes. In addition, upon T cell receptor stimulation with anti-CD3, isolated splenocytes of DSP-4 treated animals produced significantly less interferon (IFN)-gamma but not IL-2 and IL-4. The proportion of monocytes/macrophages and T cells in the spleen remained unaffected by the neurotoxin treatment, however, the percentage of natural killer cells decreased significantly. The findings suggest that a certain level of central noradrenergic tone is required for normal functioning of peripheral immune cells.
Engler
Harald
H
Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. harald.engler@uk-essen.de
Doenlen
Raphael
R
Riether
Carsten
C
Engler
Andrea
A
Besedovsky
Hugo O
HO
Del Rey
Adriana
A
Pacheco-López
Gustavo
G
Schedlowski
Manfred
M
D000704:Analysis of Variance; D000818:Animals; D001596:Benzylamines / Q000633:toxicity*; D015992:Body Mass Index; D001921:Brain / Q000166:cytology*; D017252:CD3 Complex / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016207:Cytokines / Q000378:metabolism*; D004563:Electrochemistry; D007962:Leukocytes / Q000145:classification / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D009638:Norepinephrine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D001596:Benzylamines; D017252:CD3 Complex; D016207:Cytokines; D008070:Lipopolysaccharides; D009498:Neurotoxins; C002748:noradrenalone; D014446:Tyrosine 3-Monooxygenase; C012102:DSP 4; D009638:Norepinephrine