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Testosterone and Immune Function in Primates: A Brief Summary with Methodological Considerations

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Abstract

The endocrine system serves as a mediator by which the body integrates environmental cues to organize physiological alterations, including changes in immunocompetence. Hormones are central mechanisms that contribute to the onset and timing of key life history events, the allocation of time and energy between competing functions, and in general modulate phenotypic development and variation. Here we provide a very brief review of testosterone and immunity, which highlights the physiological costs that elevated testosterone levels can incur as a result of reproductive investments. We focus primarily on nonhuman primates where possible. Although there is substantial evidence that testosterone exerts some influences on immune responses, results from in vivo studies involving human and nonhuman primates have yielded equivocal results regarding such immunomodulatory actions. There may be several reasons for this, including variation in study design, immunological measures used, levels of other hormones present, host energy status, and even social conditions. We therefore review some of these potential methodological issues, concluding that increased care must be taken to analyze seasonal variability in energy budgets, to collect an adequate number of samples from known individuals, to account for status in the dominance hierarchy when applicable, and to use multiple measures of immunity. We must also seek to understand the collaborative effects of multiple hormones (particularly dehydroepiandrosterone and estradiol) with relation to their downstream immunological effects, assessing both individual and multiplicative actions in both males and females. Such efforts would benefit from the development of additional noninvasive immune measures for primates.

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Acknowledgments

We thank Alexander Georgiev and Melissa Emery Thompson for inviting us to contribute to this special issue. In addition, we thank Alex and two anonymous reviewers for their valuable comments to previous versions of this paper.

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  1. Evolutionary Physiology and Ecology Laboratory, Department of Anthropology, Indiana University, Bloomington, IN, 47405, USA

    Sean P. Prall & Michael P. Muehlenbein

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Correspondence to Michael P. Muehlenbein.

Glossary

Androgen

Group of steroid hormones, including testosterone, utilizing specific receptors whose primary role includes the maintenance and development of male reproductive characteristics.

Antibody

Also known as immunogloublins, antibodies are crucial proteins in the immune system, which act by binding onto foreign molecules and instigating a cascade of immunological effects. There are several types, including IgA, which is primarily secreted into the oral cavity and other mucus membranes and binds to pathogens to prevent their attachment to the cell surface.

B cells

A specialized lymphocyte involved in the humoral branch of the immune system. When activated, B cells produce antibodies specific to a pathogen.

Bacterial killing assay

An in vitro assay of innate immune function, primarily related to complement proteins and various antimicrobials, where serum or saliva is cultured with a known quantity of bacteria.

Complement system

The complement system, a facet of innate immunity, is a system of plasma proteins that, when activated via several different pathways, result in immunological responses. These responses include phagocyte recruitment, increasing pathogen phagocytosis, and formation of a protein complex (membrane attack complex) that causes lysis of pathogens.

C-reactive protein

An inflammatory protein synthesized by the liver whose primary role is to signal for the removal of dead cells or pathogens.

Cortisol

A glucocorticoid produced by the adrenal gland whose primary role involves increasing plasma glucose, but also has anti-inflammatory properties and regulates immune function at several levels. Is a key component of normal stress responses.

Cytokines

Specialized protein messengers that act as signaling molecules for the immune system separated into various groups depending on function. Th-1 cytokines (pro-inflammatory) include tumor necrosis factor α (TNF-α), interferon γ (IFNγ), interleukin-1β (IL-1β), IL-2, IL-12, and others, and play a role in regulating cellular immunity. Th-2 cytokines (anti-inflammatory) are primarily involved in humoral immunity and include IL-4, IL-5, IL-6, IL-10, and others.

Dehydroepiandrosterone (DHEA)

An adrenal androgen (along with the sulfated version dehydroepiandrosterone-sulfate, or DHEA-S) whose primary role is as a precursor for the synthesis of other hormones.

Estradiol

More specifically, 17β-estradiol, is the most potent estrogen synthesized from the granulosa cells of the ovaries, whose primary role includes the development and maintenance of female reproductive physiology.

Hemolytic complement assay

An in vitro assay measuring the ability of the complement system (specifically the antibody-dependent pathway) to lyse sheep red blood cells.

Insulin-like growth factor 1 (IGF1)

A hormone produced by the liver stimulated by growth hormone, whose primary role is related to growth and development.

Lymphocyte

Specific white blood cells, including T and B cells, that play important roles in adaptive immune responses, including the release of cytokines and antibodies, and lysis of foreign cells or pathogens.

Lymphocyte proliferation assay

An assay measuring the functional ability of T and B cells to undergo mitosis in vitro in response to an exposure to a mitogen.

Lysozyme

An enzyme found in large quantities in mucous membranes that acts to rupture the cell walls of bacteria.

T cells

A specialized lymphocyte involved in cell-mediated immunity, with several different subtypes each with a different function. CD8 or cytotoxic T cells attach and destroy pathogens, CD4 or helper T cells secrete cytokines to aid in the maturation of other immunological cells, and regulatory T cells (Treg) act to suppress cell-mediated immunity after infection.

Testosterone

An androgen synthesized in the Leydig cells of the testes (as well as the adrenal glands), important in the development and maturation of secondary sexual characteristics, as well as in other various physiological systems including muscle anabolism and spermatogenesis.

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Prall, S.P., Muehlenbein, M.P. Testosterone and Immune Function in Primates: A Brief Summary with Methodological Considerations. Int J Primatol 35, 805–824 (2014). https://doi.org/10.1007/s10764-014-9752-x

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