Ex-vivo effect of dexamethasone on cytokine production from whole blood of septic patients: correlation with disease severity.
BACKGROUND
Controversial findings of former clinical trials on the effect of low dose hydrocortisone in patients with septic shock led to investigate the effect of corticosteroids on the production of cytokines from endotoxin (LPS)-stimulated whole blood.


METHODS
Whole blood from 33 septic patients was sampled within 24h alter diagnosis. Hydrocortisone was not administered during follow-up. Whole blood was stimulated with 30 ng/ml of LPS in the presence of 0.01, 0.1, 1 and 10 microM of dexamethasone. Concentrations of cytokines and of sTREM-1 were estimated in supernatants after six hours of incubation.


RESULTS
Dexamethasone inhibited LPS-stimulated release of TauNuFalpha, of IL-6, of IL-8 and of IL-10 in dose-dependent manner. A dual effect on the kinetics of release of IL-1beta and of sTREM-1 was shown. Release of IL-1beta was either decreased, what was connected with unfavorable outcome, or it was unaffected what was connected with a favorable outcome. Release of sTREM-1 was either increased, what was connected with unfavorable outcome, or it was decreased what was connected with a favorable outcome.


CONCLUSIONS
Part of the beneficiary effect of corticosteroids in sepsis may be due to an effect on the release of IL-1beta and of sTREM-1. This effect does not seem to be homogeneous for all septic patients.
4th Department of Internal Medicine, University of Athens, Medical School, Greece. giamarel@ath.forthnet.gr
Evangelos J
EJ
Giamarellos-Bourboulis
Ioanna
I
Dimopoulou
Anastasia
A
Kotanidou
Olga
O
Livaditi
Aimilia
A
Pelekanou
Stylianos
S
Tsagarakis
Apostolos
A
Armaganidis
Stylianos E
SE
Orfanos
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood / Q000276:immunology; D003907:Dexamethasone / Q000276:immunology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D011971:Receptors, Immunologic / Q000378:metabolism; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D013534:Survival; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D016207:Cytokines; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D003907:Dexamethasone