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Originally published online as doi:10.1189/jlb.0108025 on May 21, 2008

Published online before print May 21, 2008
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(Journal of Leukocyte Biology. 2008;84:915-923.)
© 2008 by Society for Leukocyte Biology

Cytokines, leptin, and stress-induced thymic atrophy

Amanda L. Gruver and Gregory D. Sempowski1

Departments of Pathology and Medicine and the Duke University Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA

1 Correspondence: Duke University Medical Center, 102 Research Dr., Rm. 1033, Global Health Research Building, Durham, NC 27710, USA. E-mail: gsem{at}duke.edu

ABSTRACT

Thymopoiesis is essential for development and maintenance of a robust and healthy immune system. Acute thymic atrophy is a complication of many infections, environmental stressors, clinical preparative regimens, and cancer treatments used today. This undesirable sequela can decrease host ability to reconstitute the peripheral T cell repertoire and respond to new antigens. Currently, there are no treatments available to protect against acute thymic atrophy or accelerate recovery, thus leaving the immune system compromised during acute stress events. Several useful murine models are available for mechanistic studies of acute thymic atrophy, including a sepsis model of endotoxin-induced thymic involution. We have identified the IL-6 cytokine gene family members (i.e., leukemia inhibitory factor, IL-6, and oncostatin M) as thymosuppressive agents by the observation that they can acutely involute the thymus when injected into a young, healthy mouse. We have gone on to explore the role of thymosuppressive cytokines and specifically defined a corticosteroid-dependent mechanism of action for the leukemia inhibitory factor in acute thymic atrophy. We also have identified leptin as a novel, thymostimulatory agent that can protect against endotoxin-induced acute thymic atrophy. This review will highlight mechanisms of stress-induced thymic involution and focus on thymosuppressive agents involved in atrophy induction and thymostimulatory agents that may be exploited for therapeutic use.

Key Words: thymopoiesis • receptor • lipopolysaccharride