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• W2954344603 abstract "488 Background: Tobacco smoking, a leading cause of preventable death, has complex effects on immune signaling. While nicotine is immunosuppressive, other constituents in tobacco smoke have pro-inflammatory effects. Since dysregulated neuroimmune signaling may contribute to compulsive drug use and associated comorbidities, the goal of this work was to compare neuroimmune responses in tobacco smokers and nonsmokers. This was accomplished using a [11C]PBR28 positron emission tomography (PET) brain imaging paradigm consisting of a baseline scan followed by a second scan acquired after injection of the classic pro-inflammatory stimulus lipopolysaccharide (LPS). Methods: Baseline scans were acquired in 16 tobacco smokers and 19 nonsmokers. A subset (8 smokers, 9 nonsmokers) participated in a second [11C]PBR28 scan 3 hours after administration of LPS (1 ng/kg, IV). PET scans were acquired with a High Resolution Research Tomograph (HRRT) for 120 min following injection of 520±195 MBq [11C]PBR28 with arterial blood sampling to measure the metabolite corrected input function. [11C]PBR28 distribution volumes (VT) were estimated with multilinear analysis in 9 regions of interest identified throughout the brain. Neuroimmune response was quantified as the percent change in [11C]PBR28 VT (ΔVT) after LPS administration from baseline. Separate linear mixed models compared baseline [11C]PBR28 VT between smokers and nonsmokers and [11C]PBR28 ΔVT between smokers and nonsmokers. Results: No significant differences in baseline [11C]PBR28 VT were observed between smokers and nonsmokers. However, a significant interaction of smoking status by region in neuroimmune response was identified (p=0.02), where [11C]PBR28 ΔVT was lower in smokers compared to nonsmokers in areas of striatum and cortex (post-hoc contrasts yielded p=0.02-0.04, uncorrected for multiple comparisons). For example, in frontal cortex (p=0.02), group ΔVT values were 33.0±11.7% and 51.4±15.4% for smokers and nonsmokers, respectively. Conclusions: While baseline [11C]PBR28 VT values were not significantly different between groups, the magnitude of response to LPS was significantly lower in smokers vs. nonsmokers, but only for some brain regions. These results provide evidence for impaired neuroimmune function in tobacco smokers compared to nonsmokers. These data also demonstrate, for the first time, sensitivity of PET imaging with a LPS challenge to detect significant differences between clinical groups, which may occur in a regionally specific pattern." @default.
• W2954344603 created "2019-07-12" @default.
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• W2954344603 date "2019-05-01" @default.
• W2954344603 modified "2023-09-23" @default.
• W2954344603 title "Imaging dynamic neuroimmune responses to LPS in tobacco smokers: a [11C]PBR28 PET study" @default.
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