Testosterone and estradiol reduce inflammation of human macrophages induced by anti-SARS-CoV-2 IgG.

Autor: Allahverdiyeva S; Center for Experimental and Molecular Medicine, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Medical Microbiology and Infection Prevention, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, the Netherlands., Geyer CE; Center for Experimental and Molecular Medicine, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, the Netherlands., Veth J; Center for Experimental and Molecular Medicine, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, the Netherlands., de Vries LM; Center for Experimental and Molecular Medicine, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, the Netherlands., de Taeye SW; Medical Microbiology and Infection Prevention, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, the Netherlands., van Gils MJ; Medical Microbiology and Infection Prevention, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, the Netherlands., den Dunnen J; Center for Experimental and Molecular Medicine, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, the Netherlands., Chen HJ; Center for Experimental and Molecular Medicine, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2024 Sep 09, pp. e2451226. Date of Electronic Publication: 2024 Sep 09.
DOI: 10.1002/eji.202451226
Abstrakt: COVID-19, the disease caused by SARS-CoV-2, particularly causes severe inflammatory disease in elderly, obese, and male patients. Since both aging and obesity are associated with decreased testosterone and estradiol expression, we hypothesized that decreased hormone levels contribute to excessive inflammation in the context of COVID-19. Previously, we and others have shown that hyperinflammation in severe COVID-19 patients is induced by the production of pathogenic anti-spike IgG antibodies that activate alveolar macrophages. Therefore, we developed an in vitro assay in which we stimulated human macrophages with viral stimuli, anti-spike IgG immune complexes, and different sex hormones. Treatment with levels of testosterone reflecting young adults led to a significant reduction in TNF and IFN-γ production by human macrophages. In addition, estradiol significantly attenuated the production of a very broad panel of cytokines, including TNF, IL-1β, IL-6, IL-10, and IFN-γ. Both testosterone and estradiol reduced the expression of Fc gamma receptors IIa and III, the two main receptors responsible for anti-spike IgG-induced inflammation. Combined, these findings indicate that sex hormones reduce the inflammatory response of human alveolar macrophages to specific COVID-19-associated stimuli, thereby providing a potential immunological mechanism for the development of severe COVID-19 in both older male and female patients.
(© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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