title: Effect of subhypnotic doses of dexmedetomidine on antitumor immunity in mice.
abstract: Dexmedetomidine, a selective alpha2 adrenergic receptor agonist, is a drug often used for sedation. Despite the high prevalence of sedating patients with tumors in intensive care settings, little is known about the effect of sedative drugs on tumor growth. We studied the effect of dexmedetomidine on antitumor immunity in mice. Subhypnotic doses of dexmedetomidine decreased interleukin (IL)-12 production from thioglycollate-induced macrophages. The treatment also decreased the ratio of the helper T lymphocytes subsets, Th1 to Th2 (Th1/Th2), in the spleen. Following subcutaneous inoculation of EL4 T-cell lymphoma cells, dexmedetomidine further decreased the splenic Th1/Th2 ratio and activity of EL4-specific cytotoxic T lymphocytes (CTLs). Finally, treatment with dexmedetomidine accelerated EL4 growth in mice. These data show that treatment of mice with subhypnotic doses of dexmedetomidine down-regulates antitumor immunity, possibly through the decreased production of IL-12 from antigen presenting cells, resulting in a Th2 shift and decreased CTL activity against EL4 in mice.
authors.affiliation: Department of Anesthesiology, Kansai Medical University, 10-15 Fumizonocho, Moriguchi, Osaka 570-8507, Japan. takefumi@wd5.so-net.ne.jp
authors.forename: Takefumi
authors.initials: T
authors.lastname: Inada
authors.forename: Atsuko
authors.initials: A
authors.lastname: Shirane
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamano
authors.forename: Makiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kambara
authors.forename: Koh
authors.initials: K
authors.lastname: Shingu
mesh_terms: D000818:Animals; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007109:Immunity / Q000187:drug effects; D018664:Interleukin-12 / Q000096:biosynthesis*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D013864:Thioglycolates / Q000494:pharmacology
chemical_list: D006993:Hypnotics and Sedatives; D013864:Thioglycolates; D018664:Interleukin-12; D020927:Dexmedetomidine