The effect of phosphodiesterase III inhibitors on human neutrophil function.
OBJECTIVE
Neutrophils play an important role in ridding the body of bacteria and cellular debris. Several neutrophil functions are thought to be regulated by inotropes that increase cellular levels of cyclic adenosine monophosphate, including phosphodiesterase (PDE) inhibitors. We have investigated the effect of amrinone, milrinone, and olprinone, type III PDE (PDE-III) inhibitors, on several human neutrophil functions.


METHODS
Prospective in vitro study.


METHODS
Academic research laboratory.


METHODS
Neutrophils isolated from 12 healthy adult volunteers.


METHODS
We measured chemotaxis, phagocytosis, reactive oxygen species production, intracellular calcium ion concentration, and cyclic adenosine monophosphate levels in neutrophils in the absence and the presence (at clinically relevant concentrations, 10 times, and 100 times those concentrations) of amrinone, milrinone, or olprinone. We also measured reactive oxygen species production under the same condition in a xanthine-xanthine oxidase system


RESULTS
None of the PDE-III inhibitors impaired neutrophil chemotaxis or phagocytosis. Amrinone at clinically relevant or higher concentrations and milrinone at high concentrations reduced superoxide, hydrogen peroxide, and hydroxyl radical levels in neutrophils and in the xanthine-xanthine oxidase system. Olprinone did not have those effects, and none of the PDE-III inhibitors had an effect on intracellular calcium ion concentration or cyclic adenosine monophosphate production in neutrophils stimulated by a chemotactic factor.


CONCLUSIONS
The ability of amrinone to scavenge reactive oxygen species at clinically relevant concentrations while not affecting neutrophil function suggests that the PDE inhibitor can be used without detriment in severely ill patients.
Mikawa
K
K
Department of Anaesthesiology, Kobe University School of Medicine, Japan.
Akamatsu
H
H
Nishina
K
K
Shiga
M
M
Maekawa
N
N
Obara
H
H
Niwa
Y
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000097:blood; D000328:Adult; D000676:Amrinone / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002474:Cell-Free System; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D000242:Cyclic AMP / Q000097:blood; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D020105:Milrinone / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D010587:Phagocytosis / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D017382:Reactive Oxygen Species; C059498:olprinone; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D020105:Milrinone; D000676:Amrinone; D002118:Calcium