Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharide-stimulated human monocytes.
We have investigated the modulating effect of steroids on the in vitro production of tumour necrosis factor (TNF) by lipopolysaccharide (LPS)-stimulated human monocytes. Dexamethasone, at concentrations ranging from 10(-8) to 10(-6) M, and cortisol, at concentrations 10(-7) and 10(-6) M, suppressed the TNF production in a dose-dependent manner. The highest concentrations of dexamethasone or cortisol reduced the TNF production to 21 +/- 2% and 48 +/- 8% of the control value, respectively. The effect of dexamethasone was time dependent, and an incubation time of 48 hr was required to reduce the TNF production to 21% of control. The effect of dexamethasone decreased when the incubation time became shorter, and the mean TNF production ranged from 49% to 72% of control when dexamethasone was added later than 8 hr before LPS addition, at the time of LPS addition, or within 1 hr after LPS addition. The magnitude of the TNF-suppressing effect of dexamethasone varied greatly from donor to donor. Only the glucocorticoids, and not the sex steroids or the mineralocorticoids, significantly reduced the TNF production.
Waage
A
A
Cell Research Laboratory, University of Trondheim, Norway.
Bakke
O
O
D000450:Aldosterone / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013196:Dihydrotestosterone; D003900:Desoxycorticosterone; D000450:Aldosterone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D006854:Hydrocortisone