PMID- 15502056
OWN - NLM
STAT- MEDLINE
DCOM- 20041126
LR  - 20210902
IS  - 0003-2999 (Print)
IS  - 0003-2999 (Linking)
VI  - 99
IP  - 5
DP  - 2004 Nov
TI  - Dobutamine inhibits phorbol-myristate-acetate-induced activation of nuclear 
      factor-kappaB in human T lymphocytes in vitro.
PG  - 1508-1515
LID - 10.1213/01.ANE.0000132976.19021.1B [doi]
AB  - Adrenergic drugs are often used for hemodynamic support of cardiac output and 
      vasomotor tone in critically ill patients. Recent evidence shows that the 
      administration of these vasoactive drugs may affect cytokine release and could 
      influence the inflammatory response. However, the mechanism of this 
      immunomodulatory effect remains unknown. The nuclear transcription factor-kappaB 
      (NF-kappaB) regulates the expression of many cytokines and plays a central role 
      in the immune response. Therefore, we examined the effects of various adrenergic 
      drugs (dobutamine, xamoterol, clenbuterol, epinephrine, norepinephrine, and 
      phenylephrine) on the activation of NF-kappaB, on the NF-kappaB-driven reporter 
      gene activity, and on the expression of the NF-kappaB target gene interleukin 
      (IL)-8. In addition, we quantified the amount of the NF-kappaB inhibitors 
      IkappaBalpha and IL-10. Here we report that dobutamine inhibited the activation 
      of NF-kappaB in primary human CD3(+) T lymphocytes. Suppression of NF-kappaB 
      involved the stabilization of its inhibitor, IkappaBalpha. The effect appears to 
      be beta(2)-receptor specific, because beta(1)-adrenergic and alpha-adrenergic 
      substances (i.e., xamoterol, epinephrine, norepinephrine, and phenylephrine) did 
      not affect NF-kappaB activation and because dobutamine-mediated inhibition of 
      NF-kappaB could be prevented by a specific beta(2)-antagonist. Our results 
      demonstrate that dobutamine is a potent and specific inhibitor of NF-kappaB, and 
      they thus provide a possible molecular mechanism for the immunomodulation 
      associated with beta-adrenergic therapy.
FAU - Loop, Torsten
AU  - Loop T
AD  - Department of Anesthesiology and Critical Care Medicine, University Hospital, 
      Freiburg, Germany.
FAU - Bross, Tobias
AU  - Bross T
FAU - Humar, Matjaz
AU  - Humar M
FAU - Hoetzel, Alexander
AU  - Hoetzel A
FAU - Schmidt, Rene
AU  - Schmidt R
FAU - Pahl, Heike L
AU  - Pahl HL
FAU - Geiger, Klaus K
AU  - Geiger KK
FAU - Pannen, Benedikt H J
AU  - Pannen BHJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Anesth Analg
JT  - Anesthesia and analgesia
JID - 1310650
RN  - 0 (Adrenergic Agents)
RN  - 0 (Adrenergic beta-Agonists)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (CD3 Complex)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Adrenergic, alpha)
RN  - 3S12J47372 (Dobutamine)
RN  - 7HE0JQL703 (Xamoterol)
RN  - 9007-49-2 (DNA)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - XTZ6AXU7KN (Clenbuterol)
SB  - IM
MH  - Adrenergic Agents/pharmacology
MH  - Adrenergic beta-Agonists/*pharmacology
MH  - *Anti-Inflammatory Agents
MH  - CD3 Complex/metabolism
MH  - Cell Nucleus/drug effects/metabolism
MH  - Clenbuterol/pharmacology
MH  - DNA/metabolism
MH  - Dobutamine/*pharmacology
MH  - Electrophoretic Mobility Shift Assay
MH  - Humans
MH  - Jurkat Cells
MH  - NF-kappa B/*antagonists & inhibitors/genetics/*metabolism
MH  - Receptors, Adrenergic, alpha/drug effects
MH  - T-Lymphocytes/drug effects/*metabolism
MH  - Tetradecanoylphorbol Acetate/*pharmacology
MH  - Xamoterol/pharmacology
EDAT- 2004/10/27 09:00
MHDA- 2004/12/16 09:00
CRDT- 2004/10/27 09:00
PHST- 2004/10/27 09:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/10/27 09:00 [entrez]
AID - 00000539-200411000-00042 [pii]
AID - 10.1213/01.ANE.0000132976.19021.1B [doi]
PST - ppublish
SO  - Anesth Analg. 2004 Nov;99(5):1508-1515. doi: 10.1213/01.ANE.0000132976.19021.1B.