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Interleukin-8 and interleukin-10, brain volume and microstructure, and the influence of calorie restriction in old rhesus macaques

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Abstract

Higher systemic levels of the proinflammatory cytokine interleukin-6 (IL-6) were found to be associated with lower gray matter volume and tissue density in old rhesus macaques. This association between IL-6, and these brain indices were attenuated by long-term 30 % calorie restriction (CR). To extend these findings, the current analysis determined if a CR diet in 27 aged rhesus monkeys compared to 17 normally fed controls reduced circulating levels of another proinflammatory cytokine, interleukin-8 (IL-8), and raised levels of anti-inflammatory interleukin-10 (IL-10). Further, these cytokines were regressed onto imaged brain volume and microstructure using voxel-wise regression analyses. CR significantly lowered IL-8 and raised IL-10 levels. Across the two dietary conditions, higher IL-8 predicted smaller gray matter volumes in bilateral hippocampus. Higher IL-10 was associated with more white matter volume in visual areas and tracts. Consuming a CR diet reduced the association between systemic IL-8 and hippocampal volumes. Conversely, CR strengthened associations between IL-10 and microstructural tissue density in the prefrontal cortex and other areas, particularly in a region of dorsal prefrontal cortex, which concurred with our prior findings for IL-6. Consumption of a CR diet lowered proinflammatory and increased anti-inflammatory cytokine concentrations, which lessened the statistical association between systemic inflammation and the age-related alterations in important brain regions, including the hippocampus.

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Acknowledgments

We give thanks for the assistance of R. Fisher and the Waisman Center for Brain Imaging. This study was supported in part by the National Institutes of Health RR000167, AG011915, AG000213, and AG043125. The study was also supported with resources and facilities at the W.S. Middleton Memorial Veterans Hospital. This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. CLC receives partial salary support from several NIH awards (AG027343, AG20166, HD057064, AI067518).

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Authors and Affiliations

  1. Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial Veterans Hospital, D-4225 Veterans Administration Hospital, 2500 Overlook Terrace, Madison, WI, 53705, USA

    A. A. Willette, A. C. Birdsill, B. B. Bendlin, R. H. Weindruch & S. C. Johnson

  2. Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, 53705, USA

    A. A. Willette, A. L. Alexander & S. C. Johnson

  3. Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA

    A. A. Willette, C. L. Coe, A. C. Birdsill, B. B. Bendlin, R. H. Weindruch & S. C. Johnson

  4. Harlow Primate Laboratory, Department of Psychology, University of Wisconsin-Madison, Madison, WI, 53715, USA

    C. L. Coe

  5. Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA

    R. J. Colman & S. C. Johnson

  6. Office of Energetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    D. B. Allison

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  1. A. A. Willette
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  2. C. L. Coe
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  8. R. H. Weindruch
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  9. S. C. Johnson
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Correspondence to S. C. Johnson.

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Willette, A.A., Coe, C.L., Birdsill, A.C. et al. Interleukin-8 and interleukin-10, brain volume and microstructure, and the influence of calorie restriction in old rhesus macaques. AGE 35, 2215–2227 (2013). https://doi.org/10.1007/s11357-013-9518-y

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