title: Repeatedly administered antidepressant drugs modulate humoral and cellular immune response in mice through action on macrophages.
abstract: Depression is associated with an altered immune response, which could be normalized by antidepressant drugs. However, little is known about the influence of antidepressants on the peripheral immune response and function of macrophages in individuals not suffering from depression. Our studies were aimed at determining the influence of antidepressant drugs on the humoral and cellular immune response in mice. Mice were treated intraperitoneally with imipramine, fluoxetine, venlafaxine, or moclobemide and contact immunized with trinitrophenyl hapten followed by elicitation and measurement of contact sensitivity by ear swelling response. Peritoneal macrophages from drug-treated mice were either pulsed with sheep erythrocytes or conjugated with trinitrophenyl and transferred into naive recipients to induce humoral or contact sensitivity response, respectively. Secretion of reactive oxygen intermediates, nitric oxide, and cytokines by macrophages from drug-treated mice was assessed, respectively, in chemiluminometry, Griess-based colorimetry and enzyme-linked immunosorbent assay, and the expression of macrophage surface markers was analyzed cytometrically. Treatment of mice with fluoxetine, venlafaxine, and moclobemide results in suppression of humoral and cell-mediated immunity with a reduction of the release of macrophage proinflammatory mediators and the expression of antigen-presentation markers. In contrast, treatment with imipramine enhanced the humoral immune response and macrophage secretory activity but slightly suppressed active contact sensitivity. Our studies demonstrated that systemically delivered antidepressant drugs modulate the peripheral humoral and cell-mediated immune responses, mostly through their action on macrophages. Imipramine was rather proinflammatory, whereas other tested drugs expressed immunosuppressive potential. Current observations may be applied to new therapeutic strategies dedicated to various disorders associated with excessive inflammation.
authors.affiliation: Department of Immunology, Jagiellonian University Medical College, PL 31-121 Krakow, Poland katarzyna.nazimek@uj.edu.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Nazimek
authors.affiliation: Students' Scientific Society, Department of Pain Treatment and Palliative Care, Jagiellonian University Medical College, PL 31-531 Krakow, Poland.
authors.forename: Michael
authors.initials: M
authors.lastname: Kozlowski
authors.affiliation: Students' Scientific Society, Department of Pain Treatment and Palliative Care, Jagiellonian University Medical College, PL 31-531 Krakow, Poland Students' Scientific Society, Department of Immunology, Jagiellonian University Medical College, PL 31-121 Krakow, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Bryniarski
authors.affiliation: Students' Scientific Society, Department of Immunology, Jagiellonian University Medical College, PL 31-121 Krakow, Poland.
authors.forename: Spencer
authors.initials: S
authors.lastname: Strobel
authors.affiliation: Students' Scientific Society, Department of Immunology, Jagiellonian University Medical College, PL 31-121 Krakow, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Bryk
authors.affiliation: Students' Scientific Society, Department of Immunology, Jagiellonian University Medical College, PL 31-121 Krakow, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Myszka
authors.affiliation: Students' Scientific Society, Department of Immunology, Jagiellonian University Medical College, PL 31-121 Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Tyszka
authors.affiliation: Students' Scientific Society, Department of Immunology, Jagiellonian University Medical College, PL 31-121 Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuszmiersz
authors.affiliation: Students' Scientific Society, Department of Immunology, Jagiellonian University Medical College, PL 31-121 Krakow, Poland.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Nowakowski
authors.affiliation: Department of Pain Treatment and Palliative Care, Jagiellonian University Medical College, PL 31-531 Krakow, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Filipczak-Bryniarska
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003866:Depressive Disorder / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D005473:Fluoxetine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D007165:Immunosuppression Therapy; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020912:Moclobemide / Q000494:pharmacology; D000069470:Venlafaxine Hydrochloride / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D016207:Cytokines; D005473:Fluoxetine; D000069470:Venlafaxine Hydrochloride; D007099:Imipramine; D020912:Moclobemide
keywords: Immune regulation; fluoxetine; imipramine; immune suppression; moclobemide; venlafaxine