Dataset Information

Safety and immunologic effects of IL-15 administration in nonhuman primates.

ABSTRACT: The administration of cytokines that modulate endogenous or transferred T-cell immunity could improve current approaches to clinical immunotherapy. Interleukin-2 (IL-2) is used most commonly for this purpose, but causes systemic toxicity and preferentially drives the expansion of CD4(+)CD25(+)Foxp3(+) regulatory T cells, which can inhibit antitumor immunity. IL-15 belongs to the gamma(c) cytokine family and possesses similar properties to IL-2, including the ability to induce T-cell proliferation. Whereas IL-2 promotes apoptosis and limits the survival of CD8(+) memory T cells, IL-15 is required for the establishment and maintenance of CD8(+) T-cell memory. However, limited data are available to guide the clinical use of IL-15. Here, we demonstrate in nonhuman primates that IL-15 administration expands memory CD8(+) and CD4(+) T cells, and natural killer (NK) cells in the peripheral blood, with minimal increases in CD4(+)CD25(+)Foxp3(+) regulatory T cells. Daily administration of IL-15 resulted in persistently elevated plasma IL-15 levels and transient toxicity. Intermittent administration of IL-15 allowed clearance of IL-15 between doses and was safe for more than 3 weeks. These findings demonstrate that IL-15 has profound immunomodulatory properties distinct from those described for IL-2, and suggest that intermittent administration of IL-15 should be considered in clinical studies.

SUBMITTER: Berger C

PROVIDER: S-EPMC2746471 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Safety and immunologic effects of IL-15 administration in nonhuman primates.

Berger Carolina C Berger Michael M Hackman Robert C RC Gough Michael M Elliott Carole C Jensen Michael C MC Riddell Stanley R SR

Blood 20090715 12

The administration of cytokines that modulate endogenous or transferred T-cell immunity could improve current approaches to clinical immunotherapy. Interleukin-2 (IL-2) is used most commonly for this purpose, but causes systemic toxicity and preferentially drives the expansion of CD4(+)CD25(+)Foxp3(+) regulatory T cells, which can inhibit antitumor immunity. IL-15 belongs to the gamma(c) cytokine family and possesses similar properties to IL-2, including the ability to induce T-cell proliferatio ...[more]

PMID: 19605850

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Project description:Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts broad effects on consciousness and perception. Since NMDA receptor antagonists induce cognitive impairments, ketamine has been used for translational research on several psychiatric diseases, such as schizophrenia. Whereas the effects of ketamine on cognitive functions have been extensively studied, studies on the effects of ketamine on simple sensory information processing remain limited. In this study, we investigated the cortex-wide effects of ketamine administration on auditory information processing in nonhuman primates using whole-cortical electrocorticography (ECoG). We first recorded ECoG from awake monkeys on presenting auditory stimuli of different frequencies or different durations. We observed auditory evoked responses (AERs) across the cortex, including in frontal, parietal, and temporal areas, while feature-specific responses were obtained around the temporal sulcus. Next, we examined the effects of ketamine on cortical auditory information processing. We conducted ECoG recordings from monkeys that had been administered anesthetic doses of ketamine from 10 to 180 min following administration. We observed significant changes in stimulus feature-specific responses. Electrodes showing a frequency preference or offset responses were altered following ketamine administration, while those of the AERs were not strongly influenced. However, the frequency preference of a selected electrode was not significantly altered by ketamine administration over time following administration, while the imbalances in the onset and offset persisted over the course of 150 min following ketamine administration in all three monkeys. These results suggest that ketamine affects the ability to distinguish between sound frequency and duration in different ways. In conclusion, future research on the NMDA sensitivity of cortical wide sensory information processing may provide a new perspective into the development of nonhuman primate models of psychiatric disorders.

Dataset Information

Safety and immunologic effects of IL-15 administration in nonhuman primates.

Publications

Safety and immunologic effects of IL-15 administration in nonhuman primates.

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