Dehydroepiandrosterone selectively inhibits production of tumor necrosis factor alpha and interleukin-6 [correction of interlukin-6] in astrocytes.
Dehydroepiandrosterone (DHEA) is a native neurosteroid with immunomodulating activity. DHEA effectively protects animals from several viral, bacterial and parasitic infections and it was suggested that its age-associated decline is related with immunosenescence. In the present study we examined the ability of DHEA to inhibit the production of inflammatory mediators by mycoplasma-stimulated glial cells and to change the course of acute central nervous system (CNS) inflammatory disease in vivo. Addition of DHEA (10 microg/ml) markedly inhibited tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) production (98 and 95%, respectively), whereas nitric oxide (NO) and prostaglandin E2 (PGE2) production was not affected. However, daily administration of 0.5 mg DHEA to mice or 5 mg to rats did not change the clinical outcome of experimental autoimmune encephalomyelitis (EAE).
Kipper-Galperin
M
M
Laboratory of Neuroimmunology, Hadassah University Hospital, Jerusalem, Israel.
Galilly
R
R
Danenberg
H D
HD
Brenner
T
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D007114:Immunization; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003687:Dehydroepiandrosterone; D003907:Dexamethasone; D015232:Dinoprostone; D003345:Corticosterone