title: Non-coplanar polychlorinated biphenyl (PCB)-induced immunotoxicity is coincident with alterations in the serotonergic system.
abstract: Attention to non-coplanar polychlorinated biphenyl (PCB) congeners in immunotoxicological research is increasing. However, the exact mechanism by which these congeners may induce immune dysfunction is still undefined. Because the serotonergic nervous system has been shown to be involved in the regulation of some immune responses, and also serves as a sensitive target for PCBs, the relationship (if any) between non-coplanar PCB exposure, immune responsiveness and the neurotransmitter serotonin (5-HT) was examined. Using bluegill sunfish (Lepomis macrochirus) as a model, changes in brain 5-HT levels, 5-HT synthesis and metabolism, and innate and cell-mediated immune parameters were evaluated following a single intraperitoneal injection of PCB 153 (5.0 or 50 μg/g body weight). Results revealed that 3 d following administration, PCB exposure decreased brain 5-HT levels (in the absence of effects on some enzymes involved in 5-HT synthesis and metabolism), increased oxyradical production by kidney phagocytes, and reduced splenic T- and B-lymphocyte proliferation. In vivo treatment of PCB-exposed fish with 5-hydroxy-L-tryptophan (the immediate precursor to 5-HT) ameliorated the observed PCB-induced immunotoxicity; in vitro treatment of immune cells from PCB-exposed fish with 5-HT failed to reverse the effects. Taken together, results from this study could suggest a link between PCB-induced alterations of brain 5-HT levels and subsequent immune dysfunction. These studies highlight the importance of indirect mechanisms of immunotoxicity, and, specifically, suggest a role for the neuroimmune axis in non-coplanar PCB-induced immune alterations.
authors.affiliation: New York University School of Medicine, Department of Environmental Medicine, Tuxedo, NY 10987, USA.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Duffy-Whritenour
authors.forename: Rebecca Z
authors.initials: RZ
authors.lastname: Kurtzman
authors.forename: Sarah
authors.initials: S
authors.lastname: Kennedy
authors.forename: Judith T
authors.initials: JT
authors.lastname: Zelikoff
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D007111:Immunity, Cellular / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007274:Injections, Intraperitoneal; D015213:Neuroimmunomodulation; D010473:Perciformes; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage*; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014364:Tryptophan / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: C518855:5-hydroxy-L-(beta-11C)tryptophan; D018490:Serotonin Agents; D012701:Serotonin; D014364:Tryptophan; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl