Summary: Tobacco smokers show signs of reduced neuroimmune responsiveness compared with nonsmokers. Preliminary PET imaging data suggest restoring neuroimmune function could help address cognitive problems and support smoking cessation.
Source: Society for Nuclear Medicine and Molecular Imaging
Preliminary research presented at the 2019 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides early evidence that tobacco smokers may have impaired neuroimmune responses compared with nonsmokers.
Tobacco use remains a leading preventable cause of illness and death worldwide. The complex chemistry of cigarette smoke produces mixed effects on the immune system: nicotine tends to suppress immune activity, while many other constituents in smoke trigger inflammation. These opposing effects complicate our understanding of how smoking affects the brain’s immune signaling, often referred to as neuroimmune function. Because altered neuroimmune signaling is increasingly implicated in compulsive drug use and in cognitive dysfunction, researchers used a targeted brain imaging approach to compare smokers and nonsmokers directly.
The study employed a dynamic positron emission tomography (PET) paradigm using the radioligand [11C]PBR28, which binds to a marker associated with neuroimmune activation. To provoke an acute immune response, investigators administered the pro-inflammatory agent lipopolysaccharide (LPS) and measured changes in brain signal before and after the challenge. This approach allowed the team to observe how the living human brain responds to an inflammatory stimulus in real time.
Participants included 16 tobacco smokers and 19 nonsmokers who completed baseline PET scans. A subset of these volunteers—eight smokers and nine nonsmokers—returned for a second scan three hours after LPS administration to measure the dynamic neuroimmune response. No significant differences were observed on baseline scans alone, indicating similar resting levels of the PET signal across groups. However, after the LPS challenge, smokers showed a significantly lower neuroimmune response in several brain regions, notably the striatum and cortical areas, compared with nonsmokers. These preliminary results suggest that tobacco smokers may have a blunted or impaired neuroimmune reactivity to an inflammatory stimulus.
Ansel T. Hillmer, PhD, assistant professor of radiology and biomedical imaging and of psychiatry at Yale University, highlighted the potential clinical significance of these findings. He noted that most therapeutic strategies under investigation for substance use disorders aim to suppress neuroinflammation, yet these preliminary data point in a different direction for tobacco smokers. “Our work suggests that restoring, rather than suppressing, certain aspects of the brain’s immune function may be beneficial for people who smoke,” Hillmer said. He added that immune dysfunction is linked to cognitive complaints commonly reported by smokers attempting to quit, and that improving neuroimmune signaling could therefore support cognitive recovery during cessation.
The study represents one of the first demonstrations that molecular imaging can detect group differences in dynamic neuroimmune responses using an LPS challenge paired with [11C]PBR28 PET. By measuring how the brain’s immune-related signal changes in response to an acute inflammatory stimulus, researchers can gain a more functional picture of neuroimmune health than is possible from static measures alone.
These preliminary results are part of an ongoing research effort. The investigators emphasize the need for larger, confirmatory studies to replicate and extend the findings, to determine how long-lasting the observed differences are, and to explore whether interventions that normalize neuroimmune responses can improve cognitive outcomes or increase the likelihood of successful smoking cessation.
Source:
Society for Nuclear Medicine and Molecular Imaging
Media Contacts:
David Harrison – Society for Nuclear Medicine and Molecular Imaging
Image Source:
The image is in the public domain.
Original Research: “Imaging Dynamic Neuroimmune Responses to LPS in Tobacco Smokers: an [11C]PBR28 PET Study,” Ansel T. Hillmer, PhD; David Matuskey, MD; Yiyun Huang, PhD; Nabeel Bill Nabulsi, PhD; Jim R. Ropchan, PhD; Richard E. Carson, PhD; Stephanie S. O’Malley, Yale University, New Haven, CT; and Kelly Patricia Cosgrove, PhD, Yale University School of Medicine and the VA Connecticut Healthcare System, West Haven, CT. Findings were presented at SNMMI’s 66th Annual Meeting, June 22–25, 2019, Anaheim, CA.