PET imaging shows no changes in TSPO brain density after IFN-α immune challenge in healthy human volunteers

Nettis, M. A., Veronese, M., Nikkheslat, N., Mariani, N., Lombardo, G., Sforzini, L., Enache, D., Harrison, N. A. ORCID: https://orcid.org/0000-0002-9584-3769, Turkheimer, F. E., Mondelli, V. and Pariante, C. M. 2020. PET imaging shows no changes in TSPO brain density after IFN-α immune challenge in healthy human volunteers. Translational Psychiatry 10 (1) , 89. 10.1038/s41398-020-0768-z

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Abstract

Depression is associated with peripheral inflammation, but its link with brain microglial activity remains unclear. In seven healthy males, we used repeated translocator protein-Positron Emission Tomography (TSPO-PET) dynamic scans with [11C]PBR28 to image brain microglial activation before and 24 h after the immune challenge interferon (IFN)-α. We also investigated the association between changes in peripheral inflammation, changes in microglial activity, and changes in mood. IFN-α administration decreased [11C]PBR28 PET tissue volume of distribution (Vt) across the brain (−20 ± 4%; t6 = 4.1, p = 0.01), but after correction for radioligand free-plasma fraction there were no longer any changes (+23 ± 31%; t = 0.1, p = 0.91). IFN-α increased serum IL-6 (1826 ± 513%, t6 = −7.5, p < 0.001), IL-7 (39 ± 12%, t6 = −3.6, p = 0.01), IL-10 (328 ± 48%, t6 = −12.8, p < 0.001), and IFN-γ (272 ± 64%, t6 = −7.0, p < 0.001) at 4–6 h, and increased serum TNF-α (49 ± 7.6%, t6 = −7.5, p < 0.001), IL-8 (39 ± 12%, t6 = −3.5, p = 0.013), and C-reactive protein (1320 ± 459%, t6 = −7.2, p < 0.001) at 24 h. IFN-α induced temporary mood changes and sickness symptoms after 4–6 h, measured as an increase in POMS-2 total mood score, confusion and fatigue, and a decrease in vigor and friendliness (all p ≤ 0.04). No association was found between changes in peripheral inflammation and changes in PET or mood measures. Our work suggests that brain TSPO-PET signal is highly dependent of inflammation-induced changes in ligand binding to plasma proteins. This limits its usefulness as a sensitive marker of neuroinflammation and consequently, data interpretation. Thus, our results can be interpreted as showing either that [11C]PBR28 is not sensitive enough under these conditions, or that there is simply no microglial activation in this model.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Springer Nature
ISSN:	2158-3188
Date of First Compliant Deposit:	4 June 2020
Date of Acceptance:	24 February 2020
Last Modified:	02 May 2023 13:33
URI:	https://orca.cardiff.ac.uk/id/eprint/132183

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