Lipopolysaccharide-induced pro-inflammatory cytokines in the brain of rats in the morphine-tolerant state.

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-alpha), interleukin-1beta (IL-1beta), 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 microg/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-alpha, IL-1beta, and IL-6 mRNA levels in the brain were determined by reverse transcriptase polymerase chain reaction. IL-1beta mRNA increased 2 h post-LPS treatment, whereas IL-6 decreased. At 16 h, TNF-alpha expression mRNA increased. These data suggest that the inflammatory response in the brain is heightened during morphine tolerance.