The effect of in vitro and in vivo dexamethasone on human neutrophil function.
There is a significant fall in PMN chemotaxis to the peptide FMLP in response to increasing concentrations of dexamethasone in vitro. The response fell in a dose related manner from a control value of 53.7 SE +/- 9.6 cells per high power field (cpf) to 47.3 SE +/- 8.1 at 10(-6) M (p less than 0.05) and 24.7 +/- 8.9 at 10(-3) M (p less than 0.025). A similar response was observed for the chemoattractants zymosan activated serum and the sol phase of purulent sputum. The effect was independent of protein synthesis or the period of incubation. Twelve milligrams of dexamethasone taken daily by 6 healthy volunteers resulted in a significant (p less than 0.025) reduction in the chemotactic response of PMN to 10(-8) M FMLP (from 29.5 +/- 1.55 to 13.7 +/- 1.8 cpf) which was apparent within 2 hours of taking the first dose. This effect was sustained for the three days on which dexamethasone was taken but returned to normal 7 days after the last dose had been administered. Dexamethasone therapy had no effect on unstimulated PMN superoxide anion production either in vitro or in vivo. The in vivo effect on neutrophil function occurred at mean serum dexamethasone concentrations of 1.26 (+/- 0.28) X 10(-7) M on day 1, 1.44 (+/- 0.15) X 10(-7) M on day 2 and 1.31 (+/- 0.13) X 10(-7) M on day 3. Thus we conclude that dexamethasone concentration which inhibit PMN chemotaxis in vivo are much lower than those required to exert the same effect in vitro.
Lomas
D A
DA
Lung Immunobiochemical Research Laboratory, General Hospital, Birmingham, U.K.
Ip
M
M
Chamba
A
A
Stockley
R A
RA
D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003907:Dexamethasone; D003513:Cycloheximide