PMID- 21245731
OWN - NLM
STAT- MEDLINE
DCOM- 20110303
LR  - 20131121
IS  - 1528-1175 (Electronic)
IS  - 0003-3022 (Linking)
VI  - 114
IP  - 2
DP  - 2011 Feb
TI  - Midazolam suppresses maturation of murine dendritic cells and priming of 
      lipopolysaccharide-induced t helper 1-type immune response.
PG  - 355-62
LID - 10.1097/ALN.0b013e3182070c1f [doi]
AB  - BACKGROUND: Dendritic cells (DCs), as antigen-presenting cells, play a key role 
      in the induction and regulation of adaptive immune response. Midazolam is 
      reported to have immunomodulatory properties that affect immune cells. However, 
      the effect of midazolam on DCs has not been characterized. We examined the 
      immunomodulatory properties of midazolam on DC-mediated immune response. METHODS: 
      After allowing murine bone marrow-derived DCs induced by granulocyte macrophage 
      colony stimulating factor to mature, we analyzed their expression of 
      costimulatory molecules (CD80 and CD86), major histocompatibility complex class 
      II molecules, and the secretion of interleukin-12 p40. In vitro, we evaluated the 
      effect of midazolam on maturing DCs in mixed cell cultures containing DCs and T 
      cells. In vivo, we investigated the contact-hypersensitivity response. RESULTS: 
      Midazolam suppressed the expression of CD80, CD86, and major histocompatibility 
      complex class II molecules from murine DCs. Treated with midazolam, DCs also 
      secreted less interleukin-12 p40. In mixed cell cultures with CD3-positive T 
      cells, midazolam-treated DCs showed less propensity to stimulate the 
      proliferation of CD3-positive T cells and the secretion of interferon-gamma from 
      CD4-positive T cells. Midazolam-treated DCs impaired the induction of 
      contact-hypersensitivity response. Treatment with ligands for peripheral 
      benzodiazepine receptor inhibited the up-regulation of CD80 during DC maturation. 
      CONCLUSION: Midazolam inhibits the functional maturation of murine DCs and 
      interferes with DC induction of T helper 1 immunity in the whole mouse. In 
      addition, it appears that the immunomodulatory effect of midazolam is mediated 
      via the action of midazolam on the peripheral benzodiazepine receptor.
FAU - Ohta, Noriyuki
AU  - Ohta N
AD  - Intensive Care Unit, Osaka University Hospital, Suita, Japan. 
      nohta753@hp-icu.med.osaka-u.ac.jp
FAU - Ohashi, Yoshifumi
AU  - Ohashi Y
FAU - Takayama, Chihiro
AU  - Takayama C
FAU - Mashimo, Takashi
AU  - Mashimo T
FAU - Fujino, Yuji
AU  - Fujino Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Anesthesiology
JT  - Anesthesiology
JID - 1300217
RN  - 0 (Anesthetics, Intravenous)
RN  - 0 (Lipopolysaccharides)
RN  - R60L0SM5BC (Midazolam)
SB  - IM
MH  - Anesthetics, Intravenous/immunology/*pharmacology
MH  - Animals
MH  - Bone Marrow Cells/drug effects/immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*drug effects/immunology
MH  - Female
MH  - Flow Cytometry
MH  - Lipopolysaccharides
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Midazolam/immunology/*pharmacology
MH  - Th1 Cells/*drug effects/*immunology
MH  - Up-Regulation/drug effects
EDAT- 2011/01/20 06:00
MHDA- 2011/03/04 06:00
CRDT- 2011/01/20 06:00
PHST- 2011/01/20 06:00 [entrez]
PHST- 2011/01/20 06:00 [pubmed]
PHST- 2011/03/04 06:00 [medline]
AID - 10.1097/ALN.0b013e3182070c1f [doi]
PST - ppublish
SO  - Anesthesiology. 2011 Feb;114(2):355-62. doi: 10.1097/ALN.0b013e3182070c1f.