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Estrogen, a double-edged sword: modulation of TH1- and TH2-mediated inflammations by differential regulation of TH1/TH2 cytokine production.

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1
Section of Surgical Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA. salemm@musc.edu

Abstract

Estrogen appears to play a central role in the immune response and immune-mediated diseases. Estrogen receptors are expressed in a variety of immunocompetent cells, including CD4(+) and CD8(+) T cells and macrophages. Clinical observations indicate that some autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, frequently remit during pregnancy but exacerbate, or have their onset during the postpartum period. Pharmacological levels of estrogen also appear to ameliorate certain autoimmune diseases. In addition, estrogen is known to suppress certain infectious diseases, as well as T cell-mediated responses toward oxazolone, keyhol lympet hemocyanin, Listeria soluble protein and purified protein derivatives. The immune basis for these phenomena is poorly understood. Based on a distinctive profile of cytokine production, data accumulated thus far have revealed modulatory effects for estrogen on the TH1-type and TH2-type cells, which represent two polarized forms of the effector specific immune response. Recent evidence indicates that estrogens inhibit the production of TH1 proinflammatory cytokines, such as IL-12, TNF-alpha and IFN-gamma, whereas they stimulate the production of TH2 anti-inflammatory cytokines, such as IL-10, IL-4, and TGF-beta. This can explain why estrogen suppresses and potentiates TH1- and TH2-mediated diseases, respectively. We hypothesize that exacerbation or suppression of inflammatory diseases by estrogen is mediated by skewing TH1-type to TH2-type response. This view represents a novel mechanism for the modulatory effect of estrogen on certain inflammatory diseases that can lead to beneficial or detrimental impacts depending on the type of immune involved. Such a concept is valuable when considering the application of combination therapies that include estrogen.

PMID:
15032646
[Indexed for MEDLINE]
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