title: Haloperidol Suppresses NF-kappaB to Inhibit Lipopolysaccharide-Induced Pro-Inflammatory Response in RAW 264 Cells.
abstract: BACKGROUND Haloperidol, a tranquilizing agent, is administered both to treat symptoms of psychotic disorders and to sedate agitated and delirious patients. Notably, haloperidol has been suggested to inhibit the immune response through unknown mechanisms. We hypothesized that the sedative modulates the immune response via NF-κB. MATERIAL AND METHODS Using flow cytometry, we analyzed the effects of haloperidol on expression CD80 and CD86 in RAW 264 cells and in primary macrophages derived from bone marrow. Secretion of interleukin (IL)-1β, IL-6, and IL-12 p40 was measured by enzyme-linked immunosorbent assay. In addition, NF-κB activation was evaluated using a reporter assay based on secretory embryonic alkaline phosphatase. Finally, synthetic antagonists were used to identify the dopamine receptor that mediates the effects of haloperidol. RESULTS Haloperidol inhibited NF-κB activation, and thereby suppressed expression of CD80, as well as secretion of IL-1β, IL-6, and IL-12 p40. CD80 and IL-6 levels were similarly attenuated by a D2-like receptor antagonist, but not by a D1-like receptor antagonist. CONCLUSIONS The data strongly suggest that haloperidol inhibits the immune response by suppressing NF-kB signaling via the dopamine D2 receptor.
authors: Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Shunsuke
authors: S
authors: Yamamoto
authors: Department of Anesthesiology and Intensive Care, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Noriyuki
authors: N
authors: Ohta
authors: Department of Anesthesiology and Intensive Care, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Atsuhiro
authors: A
authors: Matsumoto
authors: Department of Anesthesiology and Intensive Care, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Yu
authors: Y
authors: Horiguchi
authors: Department of Anesthesiology and Intensive Care, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Moe
authors: M
authors: Koide
authors: Department of Anesthesiology and Intensive Care, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Yuji
authors: Y
authors: Fujino
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000067996:RAW 264.7 Cells; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines; D007378:Interleukins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017448:Receptors, Dopamine D2; D006220:Haloperidol