Prevention of immune dysfunction and vitamin E loss by dehydroepiandrosterone and melatonin supplementation during murine retrovirus infection

Abstract

SUMMARYFemale C57BL/6 mice infected with the LP-BM5 leukaemia retrovirus developed murine acquired immune-deficiency syndrome (AIDS ). Dehydroepiandrosterone (DHEA) and melatonin (MLT ) modify immune dysfunction and prevent lipid peroxidation. We investigated whether DHEA and MLT could prevent immune dysfunction, excessive lipid peroxidation, and tissue vitamin E loss induced by retrovirus infection. Retrovirus infection inhibited the release of T helper 1 ( Th1) cytokines, stimulated secretion of Th2 cytokines, increased hepatic lipid peroxidation, and induced vitamin E deficiency. Treatment with DHEA or MLT alone, as well as together, largely prevented the reduction of B-and T-cell proliferation as well as of Th1 cytokine secretion caused by retrovirus infection. Supplementation also suppressed the elevated production of Th2 cytokines stimulated by retrovirus infection. DHEA and MLT simultaneously reduced hepatic lipid peroxidation and prevented vitamin E loss. The use of DHEA plus MLT was more effective in preventing retrovirus-induced immune dysfunction than either DHEA or MLT alone. These results suggest that supplementation with DHEA and MLT may prevent cytokine dysregulation, lipid oxidation and tissue vitamin E loss induced by retrovirus infection. Similarly, hormone supplementation also modified immune function and increased tissue vitamin E levels in uninfected mice.

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

“…If necessary, RNA was further purified by digestion using DNase I. Four micrograms of total RNA was reverse transcribed (RT) to cDNA using a GeneAmp RNA PCR kit with oligo d(T) 16 primers (PerkinElmer, Branchburg, NJ; RT reaction). PCR amplification of each cDNA target (CD3␥, IFN-␥, IL-4, IL-12 p40, TNF-␣, and inducible NO synthase (iNOS)) was performed from the same RT reaction as an internal control GAPDH.…”

“…In animal model systems, administration of DHEA enhances the ability of mice to resist experimental viral and bacterial diseases (15)(16)(17)(18)(19)(20). In humans, many chronic inflammatory diseases are associated with lower serum levels of DHEA or DHEAS (21).…”

Role of the N, N′-dimethylbiguanide metformin in the treatment of female prepuberal BALB/c mice hyperandrogenized with dehydroepiandrosterone

“…Subsequent studies established that the DHEA-PCOS murine model exhibits some of the salient features of human PCOS, such as hyperandrogenism, abnormal maturation of ovarian follicules and anovulation (Lee et al 1991, Anderson et al 1992, Henmi et al 2001. These findings, together with the fact that increasing evidence indicates that DHEA has, in addition, potent immunoregulatory functions (Meikle et al 1992, Okabe et al 1995, Hernandez Pardo et al 1998, Zhang et al 1999) led us to use the DHEA-mice model to study some aspects related to the endocrine and immune responses involved.…”

Pharmacological Countermeasures to Spaceflight-Induced Alterations of the Immune System

“…DHEA-S increases superoxide generation in primed human neutrophils in a dose-dependent fashion, thereby impacting a key bactericidal mechanism (Radford et al 2010 ) . In murine models, exogenous DHEA counteracts stress-induced glucocorticoid immunosuppression and increases the resistance of mice to viral and bacterial infections (Ben et al 1999 ;Zhang et al 1999 ) . In murine model systems of aging, DHEA appears to reverse the immunological defects seen as a consequence of aging.…”