Effects of glucocorticoids on lymphocyte metabolism.
The immunosuppressive effect of glucocorticoids has been widely reported; however, the mechanism of action of these hormones on the immune system has not been fully established. In the present study, the effect of glucocorticoids on glucose, glutamine, and pyruvate metabolism in lymph node lymphocytes was investigated. Addition of dexamethasone to the incubation medium did not alter glucose and glutamine metabolism but inhibited pyruvate utilization by 40%. This latter effect took 1 h to occur and remained for up to 6 h, even after removal of dexamethasone from the culture medium. Measurements of the activity of pyruvate dehydrogenase in lymphocytes and the rate of [1-14C]-pyruvate conversion into 14CO2 in incubated lymphocyte mitochondria demonstrated that glucocorticoids decrease pyruvate utilization by inhibiting the activity of this key regulatory enzyme. The effect of such an inhibition of pyruvate utilization on the function of cells of the immune system remains to be clarified.
Serrano
M A
MA
Department of Physiology and Biophysics, Sao Paulo University, Brazil.
Curi
R
R
Parry-Billings
M
M
Williams
J F
JF
Newsholme
E A
EA
D000818:Animals; D002478:Cells, Cultured; D002940:Circadian Rhythm; D003653:Decarboxylation; D003907:Dexamethasone / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D017208:Rats, Wistar
D011773:Pyruvates; D005973:Glutamine; D015735:Mifepristone; D003907:Dexamethasone; D019289:Pyruvic Acid; D005947:Glucose; D008797:Metyrapone