Testosterone & Immunocompetence

Discussion in 'Men's Health Forum' started by Michael Scally MD, May 11, 2018.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    No Evidence for The Immunocompetence Handicap Hypothesis in Males

    The observations that testosterone might be immunosuppressive, form the basis for the immunocompetence handicap hypothesis (ICHH). According to ICHH only high-quality individuals can maintain high levels of testosterone and afford the physiological cost of hormone-derived immunosuppression.

    The animal and human studies that attempted to support the ICHH by precisely defined impairment of immunity associated with high testosterone levels are inconclusive. Furthermore, human studies have used only selected immune functions and varying testosterone fractions.

    This is the first study examining the relationship between multiple innate and adaptive immunity and serum levels of free testosterone, total testosterone, DHT and DHEA in ninety-seven healthy men. Free testosterone and marginally DHT levels were positively correlated with the strength of the influenza post-vaccination response. Total testosterone and DHEA showed no immunomodulatory properties.

    Our findings did not support ICHH assumptions about immunosuppressive function of androgens. In the affluent society studied here, men with higher levels of free testosterone could afford to invest more in adaptive immunity. Since the hormone-immune relationship is complex and may depend on multiple factors, including access to food resources, androgens should be treated as immunomodulators rather than implicit immunosuppressants.

    Nowak J, Pawłowski B, Borkowska B, Augustyniak D, Drulis-Kawa Z. No evidence for the immunocompetence handicap hypothesis in male humans. Scientific reports 2018;8:7392. No evidence for the immunocompetence handicap hypothesis in male humans
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Gubbels Bupp MR, Jorgensen TN. Androgen-Induced Immunosuppression. Frontiers in immunology 2018;9:794. https://www.frontiersin.org/articles/10.3389/fimmu.2018.00794/full

    In addition to determining biological sex, sex hormones are known to influence health and disease via regulation of immune cell activities and modulation of target-organ susceptibility to immune-mediated damage. Systemic autoimmune disorders, such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis are more prevalent in females, while cancer shows the opposite pattern. Sex hormones have been repeatedly suggested to play a part in these biases. In this review, we will discuss how androgens and the expression of functional androgen receptor affect immune cells and how this may dampen or alter immune response(s) and affect autoimmune disease incidences and progression.
  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] testosterone is an Endogenous Regulator of BAFF and Splenic B Cell Number

    Testosterone deficiency in men is associated with increased risk for autoimmunity and increased B cell numbers through unknown mechanisms.

    Here we show that testosterone regulates the cytokine BAFF, an essential survival factor for B cells.

    Male mice lacking the androgen receptor have increased splenic B cell numbers, serum BAFF levels and splenic Baff mRNA.

    Testosterone deficiency by castration causes expansion of BAFF-producing fibroblastic reticular cells (FRCs) in spleen, which may be coupled to lower splenic noradrenaline levels in castrated males, as an α-adrenergic agonist decreases splenic FRC number in vitro.

    Antibody-mediated blockade of the BAFF receptor or treatment with the neurotoxin 6-hydroxydopamine revert the increased splenic B cell numbers induced by castration.

    Among healthy men, serum BAFF levels are higher in men with low testosterone.

    Our study uncovers a previously unrecognized regulation of BAFF by testosterone and raises important questions about BAFF in testosterone-mediated protection against autoimmunity.

    Wilhelmson AS, Lantero Rodriguez M, Stubelius A, et al. Testosterone is an endogenous regulator of BAFF and splenic B cell number. Nature Communications 2018;9:2067. Testosterone is an endogenous regulator of BAFF and splenic B cell number
  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Production of Amphiregulin And Recovery from Influenza Is Greater in Males Than Females

    Background - Amphiregulin (AREG) is an epidermal growth factor that is a significant mediator of tissue repair at mucosal sites, including in the lungs during influenza A virus (IAV) infection. Previous research illustrates that males of reproductive ages experience less severe disease and recover faster than females following infection with IAV.

    Methods - Whether males and females differentially produce and utilize AREG for pulmonary repair after IAV infection was investigated using murine models on a C57BL/6 background and primary mouse and human epithelial cell culture systems.

    Results - Following sublethal infection with 2009 H1N1 IAV, adult female mice experienced greater morbidity and pulmonary inflammation during the acute phase of infection as well as worse pulmonary function during the recovery phase of infection than males, despite having similar virus clearance kinetics.

    As compared with females, AREG expression was greater in the lungs of male mice as well as in primary respiratory epithelial cells derived from mouse and human male donors, in response to H1N1 IAVs.

    Internalization of the epidermal growth factor receptor (EGFR) was also greater in respiratory epithelial cells derived from male than female mice. IAV infection of Areg knock-out (Areg−/−) mice eliminated sex differences in IAV pathogenesis, with a more significant role for AREG in infection of male compared to female mice.

    Deletion of Areg had no effect on virus replication kinetics in either sex. Gonadectomy and treatment of either wild-type or Areg−/− males with testosterone improved the outcome of IAV as compared with their placebo-treated conspecifics.

    Conclusions - Taken together, these data show that elevated levels of testosterone and AREG, either independently or in combination, improve resilience (i.e., repair and recovery of damaged tissue) and contribute to better influenza outcomes in males compared with females.

    Vermillion MS, Ursin RL, Kuok DIT, et al. Production of amphiregulin and recovery from influenza is greater in males than females. Biology of Sex Differences 2018;9:24. Production of amphiregulin and recovery from influenza is greater in males than females