Decreased Serum Dehydroepiandrosterone Is Associated with an Increased Progression of Human Immunodeficiency Virus Infection in Men with CD4 Cell Counts of 200-499

Jacobson, Mark A.; Fusaro, Robert E.; Galmarini, M.; Lang, William

doi:10.1093/infdis/164.5.864

Cited by 76 publications

(34 citation statements)

References 19 publications

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“…Recent studies have shown that low DRIEA levels can independently predict disease progression of HIV infection to AIDS, and it was suggested that DHEA may have a therapeutic value in HIV patients (13). On the basis of our data we suggest a possible mechanism for DHEA involvement in HIV patients and a rationale for treatment: expression of HIV can be activated by TNF (7,25).…”

Section: Discussionsupporting

confidence: 58%

Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production

Danenberg

Alpert

Lustig

et al. 1992

Antimicrob Agents Chemother

120

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Recent reports have demonstrated an immunomodulating activity of dehydroepiandrosterone (DHEA) different from that described for glucocorticoids. The present study was designed to test DHEA's activity in endotoxic shock and to investigate its effect on endotoxin-induced production of tumor necrosis factor (TNF).Mortality of CD-1 mice exposed to a lethal dose of lipopolysaccharide (LPS; 800 ,ug per mouse) was reduced from 95 to 24% by treatment with a single dose of DHEA, given 5 min before LPS. LPS administration resulted in high levels of TNF, a response that was significantly blocked by DHEA, both in vivo and in vitro. DHEA treatment also reduced LPS-induced increments in serum corticosterone levels, a parameter considered not to be mediated by TNF. In another experimental model, mice sensitized with D-galactosamine, followed by administration of recombinant human TNF, were subjected to 89% mortality rate, which was reduced to 55% in DHEA-treated mice. These data show that DHEA protects mice from endotoxin lethality. The protective effect is probably mediated by reduction of TNF production as well as by effecting both TNF-induced and non-TNF-induced phenomena.Dehydroepiandrosterone (DHEA) is an abundantly secreted, weak androgenic, adrenocortical steroid hormone that is an intermediate in the biosynthesis of other hormones including testosterone and estradiol-171. Concentrations of DHEA in plasma gradually decline after the third decade of life, reaching 10 to 20% of the peak level in the e!derly (20,24).The precise biological functions of DHEA are uncertain. A growing body of evidence, both experimental and epidemiological, suggests an inverse relationship between low levels of DHEA in serum and morbidity from atherosclerotic cardiovascular disease (1, 9), cancer (10,11,26) and human immunodeficiency virus (HIV) infection (31). Moreover, low levels of DHEA were found to be independently predictive of death from any cause (1).Recent reports proposed an immunomodulating activity of DHEA. It was found to prevent dexamethasone-induced thymic involution in mice (19), increase interleukin-2 production both in vitro and in vivo (6), and prevent the development of systemic lupus erythematosus in a mouse model (18). Lymphopoiesis, but not myelopoiesis or erythropoiesis, was inhibited in irradiated mice fed with DHEA (28, 29). Although lacking an in vitro antiviral activity, DHEA was effective in protecting mice from a variety of lethal viral infections (2, 17).During the course of gram-negative infections, bacterial cell wall products, such as endotoxin (lipopolysaccharide [LPS]), are released, inducing intense pathophysiologic alterations (22). It is not LPS alone that causes the damage, but rather the host response, which may be described as an "overshoot" of the immune system. One of the major responses to LPS in vivo is the rapid production and secretion of cytokines, the soluble mediators of inflammation, like tumor necrosis factor (TNF) (3,5).LPS toxicity can be reduced by administration of potent immunosuppresi...

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Section: Discussionsupporting

confidence: 58%

Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production

Danenberg

Alpert

Lustig

et al. 1992

Antimicrob Agents Chemother

120

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“…In contrast to Christeff's ® ndings, Jacobson et al 15 reported a trend association between decreased DHEA prior to the development of KS or lymphoma. Another study by Rosenthal and colleagues 16 failed to ® nd elevated DHEA or other androgens in 10 men with KS.…”

Section: Does Testosterone Exacerbate Kaposi's Sarcoma?mentioning

confidence: 62%

Testosterone treatment of clinical hypogonadism in patients with HIV/AIDS

Rabkin

Rabkin²,

Wagner³

1997

Int J STD AIDS

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The use of testosterone to treat clinical symptoms of hypogonadism and wasting among patients with HIV/AIDS is a relatively new area of inquiry and clinical application. Outcome measures have included changes in mood, libido, energy, weight and muscle mass. The purpose of this review is to identify the questions most commonly raised about risks of testosterone therapy, to review available data which address these questions, and to discuss issues of clinical management. These include treatment indications, measurement issues, and side effects and their management.

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“…Among HIV-infected men, DHEA is used to increase energy and stamina, increase muscle mass, and even to improve the outcome of HIV infection [35]. Indeed, endogenous levels of DHEA appear to correlate with prognosis in a number of illnesses, including HIV infection [3,25], and intake of DHEA reduces manifestations of depression and improves the sense of well-being [16,28,36].…”

Section: Discussionmentioning

confidence: 99%

“…Serum concentrations of DHEAS decline with age [2] and are low in numerous disease states, including HIV infection [3] and depression [4].…”

Section: Introductionmentioning

confidence: 99%

Endocrine effects of oral dehydroepiandrosterone in men with HIV infection: a prospective, randomized, double-blind, placebo-controlled trial

et al. 2006

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Decreased Serum Dehydroepiandrosterone Is Associated with an Increased Progression of Human Immunodeficiency Virus Infection in Men with CD4 Cell Counts of 200-499

Cited by 76 publications

References 19 publications

Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production

Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production

Testosterone treatment of clinical hypogonadism in patients with HIV/AIDS

Endocrine effects of oral dehydroepiandrosterone in men with HIV infection: a prospective, randomized, double-blind, placebo-controlled trial

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