title: Desipramine administered chronically inhibits lipopolysaccharide-stimulated production of IL-1β in the brain and plasma of rats.
abstract: Nowadays, it is assumed that therapeutic efficacy of antidepressants depends, at least partly, on their anti-inflammatory properties. The present study investigated for the first time the effect of 21-day oral administration of desipramine on the lipopolysaccharide (LPS)-stimulated IL-1β concentration in the olfactory bulb, hypothalamus, frontal cortex, hippocampus and plasma of rats, and on the LPS-induced IL-1β mRNA level in the olfactory bulb. Desipramine (15mg/kg/day) reduced significantly the LPS (250 μg/kg i.p.)-induced IL-1β concentration in the olfactory bulb, hypothalamus and in plasma, and diminished the LPS effect on IL-1β mRNA in the olfactory bulb. Plasma concentration of desipramine was comparable to its therapeutic range. By using the α1/α2-adrenoceptor antagonist prazosin and the unspecific β-adrenoceptor antagonist propranolol given prior to LPS, we found that the effect of desipramine on LPS-induced IL-1β production was partially mediated by both adrenoceptors in the olfactory bulb and plasma, and that β-adrenoceptors contributed also to its effect on the stimulated IL-1β concentration in the hypothalamus. The effect of LPS on the cerebral IL-1β levels was, in part, mediated by β-adrenoceptors and, in a region-specific manner, by α1/α2-adrenoceptors. The findings provide evidence for central and peripheral anti-inflammatory activity of desipramine and confirm the impact of the noradrenergic system on IL-1β production induced by an immunostimulatory challenge.
authors.affiliation: Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland. Electronic address: eobuchowicz@sum.edu.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Obuchowicz
authors.affiliation: Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Prymus
authors.affiliation: Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Bielecka
authors.affiliation: Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Drzyzga
authors.affiliation: Department of Medical Genetics, Faculty of Pharmacy with Division of Laboratory Medicine, Sosnowiec, Medical University of Silesia in Katowice, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Paul-Samojedny
authors.affiliation: Department of Pharmacokinetics and Drug Metabolism, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Kot
authors.affiliation: Department of Pharmacokinetics and Drug Metabolism, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Władysława A
authors.initials: WA
authors.lastname: Daniel
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage* / Q000097:blood; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D003891:Desipramine / Q000008:administration & dosage* / Q000097:blood; D004334:Drug Administration Schedule; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology*; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism; D011224:Prazosin / Q000008:administration & dosage; D011433:Propranolol / Q000008:administration & dosage; D051381:Rats
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000959:Antihypertensive Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011433:Propranolol; D003891:Desipramine; D011224:Prazosin
keywords: Adrenoceptors; Desipramine; IL-1β; Lipopolysaccharide; Rat brain and plasma