Cytokines, leptin, and stress-induced thymic atrophy

Abstract: Thymopoiesis is essential for develop-ment and maintenance of a robust and healthy immune system. Acute thymic atrophy is a compli-cation of many infections, environmental stressors, clinical preparative regimens, and cancer treat-ments 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 compro-mised during acute stress events. Several useful murine models are available for mechanistic stud-ies of acute thymic atrophy, including a sepsis model of endotoxin-induced thymic involution. We have identified the IL-6 cytokine gene family mem-bers (i.e., leukemia inhibitory factor, IL-6, and oncostatin M) as thymosuppressive agents by the observation that they can acutely involute the thy-mus when injected into a young, healthy mouse. We have gone on to explore the role of thymosup-pressive cytokines and specifically defined a corti-costeroid-dependent mechanism of action for the leukemia inhibitory factor in acute thymic atrophy. We also have identified leptin as a novel, thymo-stimulatory agent that can protect against endotox-in-induced acute thymic atrophy. This review will highlight mechanisms of stress-induced thymic in-volution and focus on thymosuppressive agents in-volved in atrophy induction and thymostimulatory agents that may be exploited for therapeutic use. J