Progesterone and autoimmune disease - PubMed (original) (raw)

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Progesterone and autoimmune disease

Grant C Hughes. Autoimmun Rev. 2012 May.

Abstract

Sexual dimorphism in human immune systems is most apparent in the female predominance of certain autoimmune diseases (ADs) like systemic lupus erythematosus (SLE). Epidemiologic, observational and experimental evidence strongly suggest sex steroids are important modulators of genetic risk in human AD. In this regard, the roles of progesterone (Pg), an immunomodulatory female sex steroid, are poorly understood. Several lines of investigation indicate Pg and synthetic progestins impact risk of AD and immune-mediated injury in different ways depending on their concentrations and their engagement of various Pg receptors expressed in immune organs, immune cells or tissues targeted by immune attack. At low physiologic levels, Pg may enhance interferon-alpha (IFN-α) pathways important in SLE pathogenesis. Commonly used synthetic progestins may have the opposite effect. At pregnancy levels, Pg may suppress disease activity in rheumatoid arthritis (RA) and multiple sclerosis (MS) via inhibition of T helper type 1 (Th1) and Th17 pathways and induction of anti-inflammatory molecules. Importantly, Pg's immunomodulatory effects differ from those of estrogens and androgens. An additional layer of complexity arises from apparent interdependence of sex hormone signaling pathways. Identifying mechanisms by which Pg and other sex steroids modulate risk of AD and immune-mediated injury will require clarification of their cellular and molecular targets in vivo. These future studies should be informed by recent genetic discoveries in human AD, particularly those revealing their sex-specific genetic associations.

Copyright © 2011 Elsevier B.V. All rights reserved.

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Conflict of interest statement

Conflict-of-interest disclosure

The author has no competing financial interests to disclose.

Figures

Figure 1

Figure 1

Female:male prevalence ratios for selected autoimmune and inflammatory disorders. Shown are the means and ranges of female:male ratios (log10 transformed) compiled in a non-weighted manner from Beeson et al. [175], Whitacre [185], Cooper and Stroehla [176], McCombe et al. [4] and Jørgensen et al. [158] For those disorders with published GWAS data, reported risk associations with IRF5 or STAT4 genes shown as either detected (+) or not detected (−). GWAS data extracted from the National Human Genome Research Institute GWAS Catalog [33]. SLE, systemic lupus erythematosus; ITP, immune (idiopathic) thrombocytopenic purpura; CIDP, chronic inflammatory demyelinating polyneuropathy.

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References

    1. Baker ME. Origin and diversification of steroids: co-evolution of enzymes and nuclear receptors. Mol Cell Endocrinol. 2011;334:14–20. - PubMed
    1. Danilova N. The evolution of immune mechanisms. J Exp Zool B Mol Dev Evol. 2006;306:496–520. - PubMed
    1. Billington WD. The immunological problem of pregnancy: 50 years with the hope of progress. A tribute to Peter Medawar. J Reprod Immunol. 2003;60:1–11. - PubMed
    1. McCombe P, Greer J, Mackay I. Sexual dimorphism in autoimmune disease. Curr Mol Med. 2009;9:1058–79. - PubMed
    1. Gabbe SG, Niebyl JR, Simpson JL. Obstetrics: Normal and Problem Pregnancies. 5. Churchill Linvingstone; Philadelphia, PA: 2007.

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