title: Effect of monoamine reuptake inhibiting antidepressants on major histocompatibility complex expression on macrophages in normal rats and rats with experimental allergic neuritis (EAN).
abstract: This study examined the modulation of IFN-gamma induced MHC class I and II expression on normal Lewis rats and rats with EAN peritoneal macrophages cultured in the absence or presence of 10(-4)-10(-8) M of the 5-HT reuptake inhibiting antidepressants zimeldine, and its metabolites norzimeldine and cpp200 oxalate as well as the antidepressants clomipramine and imipramine, in addition amitriptyline, nortriptyline and maprotiline in EAN rats. In normal rats, MHC class I expression was suppressed by the antidepressants zimeldine, norzimeldine and cpp200 oxalate at concentrations up to 10(-5) M. At concentrations between 10(-6) to 10(-8) M, the same drugs significantly enhanced MHC class expression. Clomipramine at 10(-8) M and imipramine at 10(-6)-10(-7) M enhanced MHC class I expression, while the MHC class II expression was not significantly influenced by concentrations < or = 10(-5) M of these two drugs. In EAN rats, MHC class I expression was enhanced by zimeldine, cpp200, imipramine, and nortriptyline at 10(-5)-10(-8) M, amitriptyline at 10(-5)-10(-7) M as well as by norzimeldine and clomipramine at 10(-6) M-10(-8) M. However, maprotiline at 10(-4)-10(-6) M suppressed class I expression in the presence of 0.5 U/ml and 1.0 U/ml of IFN-gamma. MHC class II expression was suppressed by cpp200 and clomipramine at 10(-4)-10(-5) M in presence of 0.5 U/ml of IFN-gamma. At concentrations < 10(-5) M most tested drugs significantly enhanced IFN-gamma induced MHC class II expression. Compared to the results in normal rats, drug effects on EAN macrophages were more pronounced and reached higher levels of significance. The 5-HT reuptake inhibiting antidepressants also exerted a modulatory effect on MHC class I and II in EAN rat macrophages even in the absence of IFN-gamma. The modulatory effect of antidepressant drugs on IFN-gamma induced MHC class I and II expression may contribute to their influence on demyelinating autoimmune diseases, and may have implications for their clinical use.
authors.affiliation: Department of Neurology, Karolinska Institutet, Huddinge Hospital, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: B O
authors.initials: BO
authors.lastname: Bengtsson
authors.forename: E
authors.initials: E
authors.lastname: Mix
authors.forename: L H
authors.initials: LH
authors.lastname: Thorell
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002997:Clomipramine / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D007099:Imipramine / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008285:Major Histocompatibility Complex / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008376:Maprotiline / Q000494:pharmacology; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D009661:Nortriptyline / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D015031:Zimeldine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000639:Amitriptyline; D000928:Antidepressive Agents; D002997:Clomipramine; D007099:Imipramine; D007371:Interferon-gamma; D008376:Maprotiline; D009661:Nortriptyline; D017367:Selective Serotonin Reuptake Inhibitors; D015031:Zimeldine; C017578:norzimelidine