Dehydroepiandrosterone Antagonizes the Suppressive Effects of Dexamethasone on Lymphocyte Proliferation*

Abstract

Administration of dehydroepiandrosterone (DHEA) appears to have physiological effects opposing those of glucocorticoids in several animal models. Recently, immunomodulatory effects of treatment with DHEA have been described. This paper reports the effects of DHEA treatment on splenocyte blastogenic responses as well as thymic and spleen weights in C3H/HeN mice. Pretreatment of mice with sc DHEA (60 mg/kg.day) for 3 days in vivo antagonized the profound suppression of in vitro blastogenic responses seen in T- and B-lymphocytes after a single injection of dexamethasone (DEX; 60 mg/kg). Pretreatment with DHEA also significantly reduced dexamethasone-induced thymic and splenic atrophy. Splenic lymphocytes from DHEA-treated mice were markedly more resistant to in in vitro suppression of blastogenesis by DEX at 10(-6)-10(-8) M compared to lymphocytes from control mice. However, DHEA added to lymphocyte cultures in vitro over a concentration range from 10(-7)-10(-8) M failed to protect against suppression of mitogenic responses caused by addition of DEX to cultures. In summary, DHEA given in vivo antagonizes the suppressive actions of DEX on lymphoid target tissues in mice.

Administration of Dehydroepiandrosterone Suppresses Experimental Allergic Encephalomyelitis in SJL/J Mice

“…Plasma levels of DHEA peak in early adulthood (reaching levels of 2-4 ng/ml) and then decline through adult life (9). In adult mice, DHEA levels are ϳ1 ng/ml and they dramatically increase following parental administration of DHEA (32). In the present investigation, the A, PCR products were visualized in a 1.5% agarose gel containing 0.5 g/ml ethidium bromide; B, Levels of each target mRNA were measured by a digital image system and were presented after they were normalized with the internal control GAPDH.…”

“…NF-B consensus oligonucleotide (5Ј-AGTTGAGGG GACTTTCCCAGGC-3Ј) was purchased from Promega (Madison, WI), and nuclear factor-Y box binding (NF-Y) oligonucleotide (5Ј-GATCT GAGAATTTTCTGATTGGTTCTGGCGAGTTTGG-3Ј) (27) was synthesized at IDT (Coralville, IA) and purified by polyacrylamide gel. Doublestranded oligonucleotide probe was labeled by 32 P in a reaction containing 2 l of probe (3.5 pmol), 1 l of T4 polynucleotide kinase buffer (10ϫ),…”

Dehydroepiandrosterone Retards Atherosclerosis Formation Through Its Conversion to Estrogen

“…8 DHEA was also reported to antagonize the suppressive effects of dexamethasone on T-and B-lymphocyte proliferation in mice. 59 T lymphocytes are known to be present and to play a certain role in atherosclerosis 60 ; however, that role has not been fully established. Although the population and distribution of T cells in an atherosclerotic lesion after DHEA treatment did not show any change in our preliminary observations, the possibility of an antiatherosclerotic effect of DHEA through the receptor-mediated system of activating T lymphocytes remains to be elucidated.…”

Reduction in the incidence and severity of collagen‐induced arthritis in DBA/1 mice, using exogenous dehydroepiandrosterone

“…DHEA, however, promotes production of IL-2 (a Thl cytokine) by activated murine T cells, and reverses the suppression of blastogenic responses and IL-2 production initiated by corticosteroids (1,5). A recent study has also shown that low levels of DHEA (100 nM down to 10 pM) can synergize with lipopolysaccharide, to increase the production of the inflammatory cytokines IL-1 and tumor necrosis factor a (TNFa) by human macrophages in vitro (6).…”