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.
Staikos
Linda
L
Institute of NeuroImmune Pharmacology, Seton Hall University, 400 South Orange Ave., South Orange, NJ 07079, USA.
Malellari
Lorenc
L
Chang
Sulie L
SL
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D004361:Drug Tolerance / Q000276:immunology*; D007107:Immune System / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009294:Narcotics / Q000009:adverse effects*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009294:Narcotics; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009020:Morphine