The effects of clonidine and dexmedetomidine on human neutrophil functions.
Neutrophil functions are inhibited by various anesthetics. Clonidine and dexmedetomidine, alpha2-agonists, are often used as adjuncts to anesthesia. Thus, we conducted the current study to determine the effect of clonidine, dexmedetomidine, and xylazine at clinically (or veterinary anesthetically) relevant concentrations (and 10 and 100 times these concentrations) on several aspects of human neutrophil functions using an in vitro system. The three alpha2-agonists had no effects on chemotaxis, phagocytosis, or superoxide anion (O2-) production of neutrophils, except that the highest concentration of clonidine inhibited chemotaxis. Increases in intracellular calcium concentrations in neutrophils stimulated by chemotaxin were not influenced by clonidine, dexmedetomidine, or xylazine. Unchanged calcium concentrations may contribute to failure to modulate the neutrophil functions. In addition, these drugs did not scavenge O2- generated by the cell-free (xanthine-xanthine oxidase) system. This is the first report concerning the effect of clonidine or dexmedetomidine on human neutrophil functions. Our findings suggest that we may not have to take extra precautions in using the alpha2-agonists in patients with infection, but that we cannot expect these drugs to be prophylaxis against autotissue injuries whose pathogenesis includes activation of neutrophils.


CONCLUSIONS
Neutrophils are involved in the antibacterial host defense system and autotissue injury. We found that clinically relevant concentrations of clonidine and dexmedetomidine do not affect chemotaxis, phagocytosis, or superoxide production by human neutrophils. These findings indicate that it may not be necessary to take special care in using alpha2-agonists in patients with infection, sepsis, or systemic inflammation.
Nishina
K
K
Department of Anaesthesiology and Intensive Care Medicine, Kobe University School of Medicine, Japan. nishina@med.kobe-u.ac.jp
Akamatsu
H
H
Mikawa
K
K
Shiga
M
M
Maekawa
N
N
Obara
H
H
Niwa
Y
Y
D000759:Adjuvants, Anesthesia / Q000008:administration & dosage / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007239:Infections / Q000503:physiopathology; D020926:Medetomidine; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014991:Xylazine / Q000008:administration & dosage / Q000494:pharmacology*