Opioids significantly alter functional responses of lymphocytes following activation. The opiate Morphine, alters the Th1 to Th2 response and modulates functional responses such as cytolytic activity and T-cell proliferation. Although there has been extensive research involving morphine's effects on lymphocytes, little is known about the effects morphine has on lymphocyte trafficking. The objective of the study was to use in vivo bioluminescent imaging to determine morphine's effect on the trafficking pattern of splenocytes systemically and into the CNS either in a naïve state or following a neuroinflammatory stimulus. A neuroinflammatory response was induced by intracerebrally administering a DNA IFN-γ DNA plasmid into morphinedependent or placebo wildtype mice. Mice with or without a neurostimulus received adoptively transferred firefly luciferase transgenic splenocytes and imaged. Morphine dependence significantly altered the inherent ability of splenocytes to traffic into the spleen, and lead to non-directed chaotic trafficking throughout the animal, including into the CNS. The morphine-mediated effects on trafficking were blocked by the antagonist naltrexone. Morphine dependence intensified splenocyte infiltration into the CNS following neuroinflammation induced by IFN-γ gene transfer. The study precented determined that morphine severely altered the ability of non-activated splenocytes to home to the spleen, inducing extrasplenic trafficking thoughout the animal. In addition to altering the ability of naive splenocyte to traffic to the spleen, this study demonstrated that morphine profoundly exacerbated lymphocyte infiltration into the CNS following a neurostimulus.
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Acknowledgements Special thanks to Dr. Maxim Cheeran for his assistance in the laboratory and Dr. Ohlfest for his assistance with plasmid inoculation. Michael Olin was supported by the National Institute of Health, National Research Service Award T32 DA07097 from the National Institute on Drug Abuse, support for this study was provided by the National Institute of Health R21DA023543-01 Opiate Modulate lymphocyte Trafficking into the CNS in TB meningitis
- In vivo imaging
- Lymphocyte trafficking