Preliminary studies on the effect of dehydroepiandrosterone (DHEA) on both constitutive and phytohaemagglutinin (PHA)-inducible IL-6 and IL-2 mRNA expression and cytokine production in human spleen mononuclear cell suspensions in vitro.
In order to gain further insight into the potential immunological benefits of oral administration of DHEA we have examined its effects on the constitutive and PHA-inducible expression by human spleen cell suspensions in vitro of IL-6 and IL-2. This was studied at both the mRNA and protein levels. The quantification of specific mRNA was undertaken using commercially available quantitative polymerase chain reaction kits. These studies, which were performed on suspensions from six individual spleens, revealed that 10(-5) M DHEA did not impair the expression of IL-6 at either the mRNA or protein level, but may have slightly enhanced the latter. In contrast, IL-2 mRNA levels were increased on most occasions, whilst IL-2 secretion was decreased, albeit slightly. Additional studies revealed that cyclosporin (approx. 10(-5) M) and dexamethasone (10(-7) M) readily inhibited these responses and the production of other cytokines, including interferon-gamma and tumour necrosis factor-alpha. These preliminary studies suggest that high doses of DHEA do not readily inhibit the production of IL-6, and indeed other cytokines, by PHA-stimulated secondary human lymphoid tissue suspensions in vitro. They may also partially explain the meagre immunomodulatory effects noted in some DHEA replacement studies in humans.
Young
D G
DG
Department of Clinical and Surgical Sciences (Surgery) and Reproductive and Developmental Sciences (Clinical Biochemistry), University of Edinburgh, Royal Infirmary, Edinburgh, UK.
Skibinski
G
G
Skibinska
A
A
Mason
J I
JI
James
K
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D000276:Adjuvants, Immunologic; D003524:Cyclosporins; D016207:Cytokines; D003687:Dehydroepiandrosterone; D003907:Dexamethasone; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015850:Interleukin-6; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D000093242:Interleukin-6 Inhibitors