Abstract
Lipopolysaccharide (LPS) induces the production of inflammatory cytokines in the serum and brain; morphine has been shown to be immunosuppressive. However, we previously reported that serum levels of LPS-induced tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6) are potentiated during morphine tolerance due to the HPA axis desensitization. In this study, we examined LPS-induced cytokine production in the brain of morphine-tolerant rats. The animals were implanted with two and four morphine (75 mg) pellets on days 1 and 2, respectively. On either day 4 or 5, 250 μg/kg LPS was administered (i.p.). Animals implanted with placebo and injected with saline were used as the control. The animals were sacrificed either 16 or 2 h post-injection, respectively, and TNF-α, IL-1β, and IL-6 mRNA levels in the brain were determined by reverse transcriptase polymerase chain reaction. IL-1β mRNA increased 2 h post-LPS treatment, whereas IL-6 decreased. At 16 h, TNF-α expression mRNA increased. These data suggest that the inflammatory response in the brain is heightened during morphine tolerance.
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Acknowledgments
This study was partially supported by R01 DA07058, R21 DA019836, and K02 DA016149 to SLC.
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Staikos, L., Malellari, L. & Chang, S.L. Lipopolysaccharide-induced Pro-inflammatory Cytokines in the Brain of Rats in the Morphine-tolerant State. J Neuroimmune Pharmacol 3, 236–240 (2008). https://doi.org/10.1007/s11481-008-9111-9
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DOI: https://doi.org/10.1007/s11481-008-9111-9