Additive effects of suboptimal doses of estrogen and cortisone on the suppression of T lymphocyte dependent inflammatory responses in mice

Abstract

Many immune-mediated inflammatory diseases are treated with corticosteroids. This type of treatment is, however, often afflicted with side-effects such as osteoporosis and atherosclerosis. During the last decades also sex steroids, such as estrogens, have been shown to have immunoregulatory properties. In this report we studied the effect of combined treatment with suboptimal doses of dexamethasone and estradiol on T lymphocyte mediated delayed type hypersensitivity (DTH), granulocyte-mediated inflammatory responses, immunoglobulin production and antigen specific antibody responses in mice. The results show that the two hormones display additive effects on suppression of DTH. In contrast, such additive effects were not observed in granulocyte-mediated inflammation. B lymphocyte activity, measured by immunoglobulin production and antigen-specific antibody responses, were increased after exposure to estradiol and suppressed by dexamethasone. In mice treated with both hormones the up regulation of B lymphocytes was still evident. The results could indicate the potential to use combinations of corticosteroids and estrogen in the treatment of T lymphocyte dependent rheumatic diseases such as rheumatoid arthritis (RA). In addition, the B lymphocyte stimulation by estrogen in cortisone exposed mice stimulate to future studies in humans if estrogen containing contraceptives or post menopausal hormone treatment could have triggering effects in patients with immune complex mediated diseases also when they are on corticosteroid treatment.

β-Estradiol Suppresses T Cell-Mediated Delayed-Type Hypersensitivity through Suppression of Antigen-Presenting Cell Function and Th1 Induction

“…For example, it possesses suppressive effects on the delayed-type hypersensitivity (DTH) response to oxazolone [1, 2, 3], keyhole limpet hemocyanin [4], collagen [5]and Listeria monocytogenes soluble antigen (Ag) [6]in mice, and to candida Ag in humans [7]. Estrogen receptor has been reported to be expressed by macrophages [8]and CD8+ T cells [9].…”

Androgens and the Immunocompetence Handicap Hypothesis: Unraveling Direct and Indirect Pathways of Immunosuppression in Song Sparrows

“…Another indirect pathway not yet tested is the possibility that T is converted to estrogenic metabolites locally in immune cells by the enzyme aromatase, leading to immunosuppression via activation of estrogen receptors. Administration of estradiol generally enhances humoral immunity but can suppress cell-mediated immune function (Erbach and Bahr 1991;Carlsten et al 1996;Salem et al 2000). Thus, separation of these direct and indirect mechanisms affecting immunocompetence is integral to our understanding of T's influence on in vivo immune function and, ultimately, sexual signaling (Poiani et al 2000).…”

Effects of the Dichloromethane Fraction of Dipsaci Radix on the Osteoblastic Differentiation of Human Alveolar Bone Marrow-Derived Mesenchymal Stem Cells

“…The primary purpose in searching for novel stimuli to induce osteogenic differentiation is to identify products with reduced side effects. Glucocorticoids are used to treat autoimmune and inflammatory diseases, including arthritis, asthma, multiple sclerosis, and systemic lupus erythematosis, 33) but long-term administration of glucocorticoids has undesired side effects, including immunosuppression 7,35) and osteoporosis with severe bone loss, and increased risk of fracture.…”

“…DEX is the primary stimulant used for in vitro induction of osteoblast differentiation from MSCs, 6) but DEX has a number of drawbacks, 3,7) including immunosuppressive effects, which limit its potential applications. Therefore, alternative inductive stimuli can serve as additional tools for examining MSCs for potential clinical applications.…”