Hormonal Regulation of the Age‐Associated Decline in Immune Function<sup>a</sup>

Kelley, Keith W.; Brief, Susan; Westly, Hollie J.; Novakofski, J.; Bechtel, Peter J.; Šimon, Jan; Walker, Edwin Ruthven

doi:10.1111/j.1749-6632.1987.tb35750.x

Cited by 25 publications

(8 citation statements)

References 27 publications

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“…There are good reasons to expect thymic development to be responsive to the local ecology. The thymus receives input from all the major neuroendocrine axes, and in turn provides feedback that modulates neuroendocrine and thymic activity (Fabris et al, 1989;Grossman, 1994;Kelley et al, 1987). Growth, sexual maturation and reproduction, nutrition, and stress have all been shown to influence thymic activity, and therefore potentially shape its development.…”

Section: Childhoodmentioning

confidence: 99%

Life history theory and the immune system: Steps toward a human ecological immunology

McDade¹

2003

Am. J. Phys. Anthropol.

284

305

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KEY WORDSimmunology; human biology; growth and development; evolutionary theory; infectious disease ABSTRACTWithin anthropology and human biology, there is growing interest in immune function and its importance to the ecology of human health and development. Biomedical research currently dominates our understanding of immunology, and this paper seeks to highlight the potential contribution of a population-based, ecological approach to the study of human immune function. Concepts from life-history theory are applied to highlight the major challenges and demands that are likely to shape immune function in a range of ecological contexts. Immune function is a major component of maintenance effort, and since resources are limited, trade-offs are expected between investment in maintenance and other critical life-history functions involving growth and reproduction. An adaptationist, life-history perspective helps make sense of the unusual developmental trajectory of immune tissues, and emphasizes that this complex system is designed to incorporate information from the surrounding ecology to guide its development. As a result, there is substantial population variation in immune development and function that is not considered by current biomedical approaches. In an attempt to construct a framework for understanding this variation, immune development is considered in relation to the competing life-history demands that define gestation, infancy, childhood, adolescence, and adulthood. Each life stage poses a unique set of adaptive challenges, and a series of hypotheses is proposed regarding their implications for immune development and function. Research in human ecological immunology is in its earliest stages, but this is a promising area of exploration, and one in which anthropology is wellpositioned to make important contributions. Yrbk Phys Research on human immune function has proliferated in the past 25 years, leading to fundamental insights into basic physiology, as well as strategies for the prevention and treatment of a wide range of diseases. The complexity of the immune system is daunting, and current biomedical research elaborates this complexity by focusing almost exclusively on cellular-and molecular-level processes. The majority of this research uses animal models, with human research participants drawn primarily from clinical settings. Complementary population-based research in international health has observed consistent, bidirectional associations between undernutrition and infectious morbidity, sparking interest in immunocompetence as a potentially important mediator (Chandra, 1988;Gershwin et al., 2000;Hoffman-Goetz, 1986;Pelletier et al., 1995;Suskind and Tontisirin, 2001).The significance of these contributions should not be overlooked, but something is missing. Human physiological systems are products of natural selection, designed to develop and function in whole organisms that are integral components of surrounding social and physical environments (Oyama, 1985;Williams and Nesse, 1991). The immune s...

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Section: Childhoodmentioning

confidence: 99%

Life history theory and the immune system: Steps toward a human ecological immunology

McDade¹

2003

Am. J. Phys. Anthropol.

284

305

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“…We showed that injection of GH in aging animals induced an upregulation of IL‐6 production by thymocytes 18. Although in vivo GH treatment can augment IL‐2 secretion by peripheral T cells,19 data on thymocytes are lacking. In a second vein, fetal calf thymocytes treated ex vivo with GH exhibited increased transcript levels of IL‐1α, IL‐1β, IL‐6, and GM‐CSF 20…”

Section: Growth Hormone Upregulates Hormonal and Cytokine Production mentioning

confidence: 90%

In Vivo Effects of Growth Hormone on Thymic Cells

Savino

Smaniotto

Binart

et al. 2003

Annals of the New York Academy of Sciences

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Increasing evidence has placed the thymus as a target for neuroendocrine control. Herein we review the pleiotropic effects of growth hormone (GH) on this primary lymphoid organ, with emphasis on data derived from in vivo experiments. A series of results strongly indicate that GH enhances thymocyte proliferation in both rodents and humans. Moreover, in vivo treatment with GH enhances interleukin (IL)-6 production by mouse thymocytes, and ex vivo experiments show that production of other cytokines, such as IL-1 and GM-CSF, is also augmented. In a second vein, GH exerts a modulatory role on thymic hormone production, particularly the secretion of thymulin. In GH-treated animals as well as GH-transgenic mice, thymulin secretion is enhanced. In acromegalic patients we found higher levels of thymulin secretion, whereas the opposite was seen in dwarf mice and GH receptor knockout animals. Developing T cell migration is also under GH influence. Recombinant GH was found to increase human T cell engraftment in the thymus of SCID mice. Moreover, ex vivo thymocyte traffic into and out of thymic nurse cell complexes is enhanced after GH treatment. Lastly, we show that thymocyte export in vivo is modulated by GH, which favors the homing of CD4(+) recent thymic emigrants towards lymph nodes. In conclusion, the possibility that GH improves in vivo thymic functions, including thymocyte proliferation and migration, points to this molecule as a potential therapeutic adjuvant in T cell associated immunodeficiencies.

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“…Implantation of an epithelial cell line derived from the pituitary was shown to reverse thymic involution in aged rats [50,51], an effect which may be due to the growth hormone produced by these cells. Analysis of the effect of testosterone also revealed an intricate involvement with thymic cellularity.…”

Section: Reversal Of Thymic Atrophymentioning

confidence: 99%

Immunosenescence: potential causes and strategies for reversal

Aspinall

Andrew

2000

Biochemical Society Transactions

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Age-related deterioration in immune function has been recognized in many species. In humans the clinical manifestation of such immune dysfunction is age-related increases in the susceptibility to certain infections and in the incidence of some autoimmune disease and certain cancers. Laboratory investigations reveal age-related changes in the peripheral T cell pool, in the predominant phenotype, cytokine production profiles, signalling function and in replicative ability following stimulus with antigen, mitogens or anti-CD3 antibody. These changes in the properties of peripheral T cells are thought to be causally linked to an age-associated involution in the thymus. Our analysis reveals that thymic involution is due to a change in the thymic microenvironment linked to a reduction in the level of available interleukin 7. Treatment with interleukin 7 leads to a reversal of thymic atrophy with increased thymopoiesis. This provides the potential to reverse the immune dysfunction seen in the peripheral T cell pool by replacing old cells with new output generated in the thymus. Problems to overcome in order for such an experimental therapy to be successful require careful analysis in order to provide an optimal strategy to ensure that new T cell emigrants from the thymus have a broad range of specificities and are able to enter the peripheral T cell pool.

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Hormonal Regulation of the Age‐Associated Decline in Immune Function^a

Cited by 25 publications

References 27 publications

Life history theory and the immune system: Steps toward a human ecological immunology

Life history theory and the immune system: Steps toward a human ecological immunology

In Vivo Effects of Growth Hormone on Thymic Cells

Immunosenescence: potential causes and strategies for reversal

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Hormonal Regulation of the Age‐Associated Decline in Immune Functiona

Cited by 25 publications

References 27 publications

Life history theory and the immune system: Steps toward a human ecological immunology

Life history theory and the immune system: Steps toward a human ecological immunology

In Vivo Effects of Growth Hormone on Thymic Cells

Immunosenescence: potential causes and strategies for reversal

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Product

Resources

About

Hormonal Regulation of the Age‐Associated Decline in Immune Function^a