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Drug Alcohol Depend. 2013 Sep 1;132(1-2):38-46. doi: 10.1016/j.drugalcdep.2012.12.022. Epub 2013 Jan 23.

Involvement of the NLRP3 inflammasome in the modulation of an LPS-induced inflammatory response during morphine tolerance.

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1
Institute of Neuroimmune Pharmacology, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA.

Abstract

BACKGROUND:

Morphine is widely used for its analgesic effects. In addition to its high potential for addiction and tolerance, morphine also induces immunosuppression. Inflammasomes, NLRP3 being the most characterized, is a platform for activation of pro-inflammatory cytokines, particularly IL-1β. We have explored the effects of lipopolysaccharide (LPS) during morphine tolerance on expression of the NLRP3 inflammasome and related inflammatory genes.

METHODS:

Morphine-pellet administration was used to induce morphine tolerance in F344 rats. Control rats were given a placebo. On day 5, the animals received either saline or 250 μg/kg LPS. LPS-induced protein expression of TNF-α, IL-1β, and IL- 6 was examined in the spleen of rats with and without morphine tolerance. A PCR array was used to examine LPS-induced expression of 84 inflammasome-related genes with and without morphine tolerance.

RESULTS:

LPS-induced IL-1β and TNF-α protein expression was significantly lower in the spleen of the morphine-tolerant animals than in the placebo-control animals. In response to LPS, expression of 27 genes, including NLRP3, TNF-α, IL-1β, and IL-6, was significantly increased, and expression of 3 genes was significantly decreased in both the morphine-tolerant and placebo-control groups compared to the saline-treated animals. However, there was only a 2.7-fold increase in NLRP3 expression in response to LPS in the morphine-tolerant rats compared to a 4.5-fold increase in the placebo-control animals.

CONCLUSION:

Our data indicate that, in the morphine-tolerant state, LPS-induced expression of NLRP3 is suppressed and cytokine/chemokine expression is inhibited, which may be one of the mechanisms involved in morphine-induced immunosuppression.

KEYWORDS:

Chemokine; Cytokine; Morphine tolerance; NLRP3 inflammasome

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