title: Haloperidol suppresses murine dendritic cell maturation and priming of the T helper 1-type immune response.
abstract: BACKGROUND
  Haloperidol has immunomodulatory effects when used to treat patients with schizophrenia and also is used to sedate critically ill patients in the intensive care unit. Although the mechanism by which haloperidol affects immune function is unclear, one possibility is that it alters dendritic cell (DC) function. DCs are potent antigen-presenting cells that influence the activation and maturation of T lymphocytes. In this study, we investigated the in vitro and in vivo immunomodulatory effects of haloperidol on DC-mediated immune responses.
  
  
  METHODS
  Using bone marrow-derived DCs in cell culture, we evaluated the effect of haloperidol on expression of costimulatory molecules (CD80 and CD86), major histocompatibility complex class ΙІ molecules, and the DC maturation marker CD83. DC culture supernatants also were evaluated for interleukin-12 p40 levels. In addition, we analyzed the effect of haloperidol on a mixed cell culture containing DCs and lymphocytes and measured the secretion of interferon-γ in the culture supernatants. We also assessed the in vivo effects of haloperidol on hapten-induced contact hypersensitivity responses.
  
  
  RESULTS
  Haloperidol inhibited the expression of CD80, CD86, major histocompatibility complex class ΙІ, and CD83 molecules on DCs and the secretion of interleukin-12p40 in DC culture supernatants. In mixed cell cultures containing both T cells (CD4 and CD8α) and DCs, haloperidol-treated DCs suppressed the proliferation of allogeneic T cells and effectively inhibited the production of interferon-γ. In vivo, haloperidol reduced hapten-induced contact hypersensitivity responses. Furthermore, an antagonist to D2-like receptor suppressed the maturation of DCs in a manner similar to haloperidol.
  
  
  CONCLUSIONS
  The results of our study suggest that haloperidol suppresses the functional maturation of DCs and plays an important role in the inhibition of DC-induced T helper 1 immune responses in the whole animal. Furthermore, the effect of haloperidol on DCs may be mediated by dopamine D2-like receptors. Together, these results demonstrate that administration of haloperidol suppresses DC-mediated immune responses.
authors: From the *Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; and †Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Atsuhiro
authors: A
authors: Matsumoto
authors: Noriyuki
authors: N
authors: Ohta
authors: Yukiko
authors: Y
authors: Goto
authors: Yozo
authors: Y
authors: Kashiwa
authors: Shunsuke
authors: S
authors: Yamamoto
authors: Yuji
authors: Y
authors: Fujino
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000187:drug effects; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use*; D006241:Haptens / Q000737:chemistry; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D014150:Antipsychotic Agents; D006241:Haptens; D053762:Interleukin-12 Subunit p40; D017448:Receptors, Dopamine D2; D006220:Haloperidol