The Effect of Testosterone on Cytokine Production in the Specific and Non‐specific Immune Response

Posma, Elske; Moes, Hendrik; Heineman, Maas Jan; Faas, Marijke M.

doi:10.1111/j.1600-0897.2004.00216.x

Cited by 63 publications

(47 citation statements)

References 23 publications

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“…These results are consistent with studies in which men with elevated serum testosterone levels exhibited the lowest levels of antibody and inflammatory cytokines following viral infection (20,21). Among men infected with HCV, each 1 ng/ml increase in total serum testosterone has been associated with a 27% increase in risk of advanced fibrosis and 16% increase in risk of advanced inflammatory activity (22).…”

Section: Discussionsupporting

confidence: 80%

Relationship between sex hormones and RIG-I signaling in peripheral blood mononuclear cells of patients infected with hepatitis C virus

Wang

Zhang

Yang

2017

Experimental and Therapeutic Medicine

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Abstract. It has previously been suggested that men and women demonstrate differing immune responses to hepatitis C virus (HCV) infection, resulting in the investigation of the role of sex hormones and if they influence the anti-HCV response. The present study aimed to examine if hormone levels were associated with interferon (IFN) signaling pathways in peripheral blood mononuclear cells of 131 patients infected with HCV and 113 healthy controls. HCV infection was diagnosed based on the presence of anti-HCV antibodies and HCV RNA in serum. Expression of testosterone and estrogen was measured at the protein level using a competitive chemiluminescence immunoassay, and at the mRNA level using reverse transcription-quantitative polymerase chain reaction. HCV-infected males had increased levels of estrogen and a decreased ratio of testosterone to estrogen compared with healthy male controls (all P<0.001). HCV-infected patients demonstrated a significantly decreased expression of IFN and retinoic acid-induced gene protein I (RIG-I), RIG-I mRNA compared with controls. Pearson correlation analysis revealed that among males, levels of RIG-I correlated with levels of IFN-β mRNA (r=0.460), testosterone (r=-0.500), and the ratio of testosterone to estrogen (r=-0.477; all P<0.001). However, levels of RIG-I did not correlate with levels of IFN-α mRNA (r=0.158) or estrogen (r=0.173; both P>0.05). These results suggested that testosterone or the ratio of testosterone to estrogen may inhibit RIG-I signaling and thereby influence immune responses to HCV infection. IntroductionHepatitis C virus (HCV), a single-strand RNA virus of the Flaviviridae family, infects approximately 170 million people worldwide (1). HCV replication in infected individuals triggers an innate immune response that is often ineffective: As many as 80% of HCV-infected patients cannot eliminate the virus and develop chronic hepatitis, cirrhosis, and even liver cancer (2). Innate immune responses to HCV infection differ between men and women (3-5), leading to the question of whether sex hormones may influence these responses.Innate immune responses are induced when pattern recognition receptors (PRRs), which are expressed on immune cells, especially antigen-presenting cells, recognize viral genetic material (6). PRRs include Rig-like helicase receptors, NOD-nucleotide binding oligomerization domain-like receptors and Toll-like receptors. PRRs trigger signaling pathways that induce the production and release of cytokines such as the type I interferons IFN-α and IFN-βThe central PRR activated in response to RNA virus infection is retinoic acid-induced gene protein I (RIG-I), a 5'-triphosphorylated, uncapped RNA-binding DexD/H-box helicase (7). After binding to viral RNA, RIG-I induces a host response in which the amino-caspase activation and recruitment domains (CARDs) interact with the amino-terminal CARD of the IFN-β promoter-stimulator 1 (IPS-1) (7).The present study explored whether differences in sex hormone levels between men and women may lead to differenc...

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Section: Discussionsupporting

confidence: 80%

Relationship between sex hormones and RIG-I signaling in peripheral blood mononuclear cells of patients infected with hepatitis C virus

Wang

Zhang

Yang

2017

Experimental and Therapeutic Medicine

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“…Here, upregulation of IL-12 signaling in men exposed to IP trauma indicates immune priming that may promote inflammation. With respect to sex dimorphism, increased percentage of IL-12 producing monocytes and lymphocytes in response to physiological concentrations of testosterone has been reported in men compared to women (Posma et al, 2014). Taken together, these distinct biological perturbations all align with a common pro-inflammatory pathology across sex and modes of trauma in PTSD.…”

Section: Discussionmentioning

confidence: 92%

PTSD Blood Transcriptome Mega-Analysis: Shared Inflammatory Pathways across Biological Sex and Modes of Trauma

Breen

Tylee

Maihofer

et al. 2017

Neuropsychopharmacol.

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Transcriptome-wide screens of peripheral blood during the onset and development of posttraumatic stress disorder (PTSD) indicate widespread immune dysregulation. However, little is known as to whether biological sex and the type of traumatic event influence shared or distinct biological pathways in PTSD. We performed a combined analysis of five independent PTSD blood transcriptome studies covering seven types of trauma in 229 PTSD and 311 comparison individuals to synthesize the extant data. Analyses by trauma type revealed a clear pattern of PTSD gene expression signatures distinguishing interpersonal (IP)-related traumas from combat-related traumas. Co-expression network analyses integrated all data and identified distinct gene expression perturbations across sex and modes of trauma in PTSD, including one wound-healing module downregulated in men exposed to combat traumas, one IL-12-mediated signaling module upregulated in men exposed to IP-related traumas, and two modules associated with lipid metabolism and mitogen-activated protein kinase activity upregulated in women exposed to IP-related traumas. Remarkably, a high degree of sharing of transcriptional dysregulation across sex and modes of trauma in PTSD was also observed converging on common signaling cascades, including cytokine, innate immune, and type I interferon pathways. Collectively, these findings provide a broad view of immune dysregulation in PTSD and demonstrate inflammatory pathways of molecular convergence and specificity, which may inform mechanisms and diagnostic biomarkers for the disorder.

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“…The IFA also confirmed the finding obtained by the PRNT of a gender-specific immune response. The reason for the stronger immune response in men than in women after YFV vaccination remains unclear even though the phenomenon is well known (15,17).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of an Indirect Immunofluorescence Assay for Detection of Immunoglobulin M (IgM) and IgG Antibodies against Yellow Fever Virus

Niedrig

Kürsteiner

Herzog

et al. 2008

Clin Vaccine Immunol

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The first commercial indirect immunofluorescence assay (IFA) using Euroimmun Biochip technology was evaluated for the serodiagnosis of immunoglobulin G (IgG) and IgM antibodies against yellow fever virus (YFV) and was compared with the plaque reduction neutralization test (PRNT), which is currently the gold standard test for YFV. An overall correlation between the tests of 98.7% was established based on the analysis of 150 sera from individuals after vaccination with the 17D yellow fever vaccine. The sensitivity and specificity, calculated using the 150 sera from vaccinees and 150 sera from healthy blood donors, were 95% and 95%, respectively, for the IgG IFA and 94% and 97% for the IgM IFA. Antibody titers found in the PRNT correlated poorly with the IgM and IgG titers detected by IFA. The analysis of preexisting heterologous flaviviral immunity revealed the presence of antibodies reactive with YFV, tick-borne encephalitis virus, West Nile virus, Japanese encephalitis virus, and dengue virus serotypes 1 to 4 in 20 out of the 150 vaccinees. The indirect IFA showed that nine of these individuals with previous flaviviral exposure who received 17D vaccine failed to produce detectable IgM antibodies. Despite this preexisting immunity, all vaccinees developed protective immunity as detected by PRNT and anti-YFV IgG antibodies as detected by IFA. The high specificity and sensitivity of the IFA make it a useful tool for rapid diagnosis of yellow fever during outbreaks, for epidemiological studies, and for serosurveillance after vaccination.

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The Effect of Testosterone on Cytokine Production in the Specific and Non‐specific Immune Response

Abstract: The increased percentage of IL-12- and IL-1beta-producing monocytes in males compared with females in vivo may be induced by testosterone, as the in vitro percentage of IL-12- and IL-1beta-producing monocytes is increased after incubation with physiological concentrations of testosterone.

Cited by 63 publications

References 23 publications

Relationship between sex hormones and RIG-I signaling in peripheral blood mononuclear cells of patients infected with hepatitis C virus

Relationship between sex hormones and RIG-I signaling in peripheral blood mononuclear cells of patients infected with hepatitis C virus

PTSD Blood Transcriptome Mega-Analysis: Shared Inflammatory Pathways across Biological Sex and Modes of Trauma

Evaluation of an Indirect Immunofluorescence Assay for Detection of Immunoglobulin M (IgM) and IgG Antibodies against Yellow Fever Virus

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