Cytokine Dysregulation and Increased Oxidation Is Prevented by Dehydroepiandrosterone in Mice Infected with Murine Leukemia Retrovirus

Abstract

The effects of murine leukemia retrovirus infection on production of cytokines was investigated in mice fed different doses of dehydroepiandrosterone (DHEA). Young C57BL/6 female mice were injected with LP-BM5 murine retrovirus or were kept as uninfected controls. Two weeks later, each group was divided into subgroups: fed unsupplemented AIN 93 diet as the control, or diets supplemented with 0.02% DHEA (0.9 mg/mouse/day) or 0.06% DHEA (2.7 mg/mouse/day). The uninfected mice supplemented with 0.06% DHEA showed a significant (P < 0.05) increase in interleukin-2 (IL-2) and gamma-interferon (IFN-gamma) production, and hepatic vitamin E levels. Retroviral infection induced severe oxidative stress that was reduced by DHEAS supplementation in retrovirally infected mice. DHEA supplementation prevented the retrovirus-induced loss of cytokines (IL-2 and IFN-gamma) secretion by mitogen stimulated spleen cells. DHEA also suppressed the production of cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) by T helper 2 (Th2) cells which were otherwise stimulated by retrovirus infection. Thus, immune dysfunction and increased oxidation induced by murine retrovirus infection were largely prevented by DHEA.

Effects of Combined Bacille Calmette-Guérin and Dehydroepiandrosterone Treatment on Established Asthma in Mice

“…Th1 cells secrete IFN-γ [15], and Treg cells secrete IL-10 and transforming growth factor-β [4], thereby conferring protection against Th2-associated allergic airway reactions. DHEA also induces Th1 [5] and Treg [6] immune responses. In addition, DHEA antagonizes glucocorticoid-induced deviation of the immune response towards a Th2 cytokine profile, probably through peroxisome proliferatoractivated receptor α [16].…”

“…In this context, many studies have shown that bacille Calmette-Guérin (BCG) and other mycobacterial infections suppress allergy and asthma, most likely through Th1 [2,3] or Treg [4] immune cell responses. In addition, adrenal androgen dehydroepiandrosterone (DHEA) has also been shown to increase the production of Th1 cytokine interferon (IFN)-γ [5] and Treg cytokine interleukin (IL)-10 [6], and suppress asthma in mice [7]. Fortunately, these promising therapeutic modalities that intervene in the early stages of the pathogenic immune process of asthma have been used for many years to prevent tuberculosis and to remedy other diseases, respectively.…”

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

“…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).…”

Pharmacological Countermeasures to Spaceflight-Induced Alterations of the Immune System

“…In vitro studies (Du et al 2001 ;Powell and Sonnenfeld 2006 ) showed that DHEA may be an important factor for increasing TH2 cytokine synthesis, which encourage vigorous antibody production and are commonly associated with antibody responses important for resisting infection, and decreasing TH1 and proinfl ammatory cytokine production. However, DHEA has shown an opposite effect in vivo in which a TH2 downregulation (or TH1 upregulation) associated with DHEA administration has been found in old or retrovirus-infected mice (Inserra et al 1998 ;Zhang et al 1999 ;Araghi-Niknam et al 1997 ) . These discrepancies may refl ect differences in assays used to determine DHEA effects on cytokine production or differences in animals used.…”