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Morphine enhances interleukin‐12 and the production of other pro‐inflammatory cytokines in mouse peritoneal macrophages
Author(s) -
Peng Xiaohui,
Mosser David M.,
Adler Martin W.,
Rogers Thomas J.,
Meissler Joseph J.,
Eisenstein Toby K.
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.68.5.723
Subject(s) - cytokine , morphine , lipopolysaccharide , tumor necrosis factor alpha , naltrexone , peritoneal cavity , pharmacology , interleukin , biology , medicine , endocrinology , microbiology and biotechnology , receptor , immunology , opioid , anatomy
In this study we investigated the capacity of morphine to modulate expression of cytokines in peritoneal macrophages. Mice were implanted subcutaneously with a 75‐mg morphine slow‐release pellet, and 48 h later resident peritoneal macrophages were harvested. Control groups received placebo pellets, naltrexone pellets, or morphine plus naltrexone pellets. Adherent cells were stimulated with lipopolysaccharide (LPS: 10 μg/mL) plus interferon‐γ (IFN‐γ: 100 units/mL) to induce cytokine production. After 24 h RNA was extracted for analysis of cytokine mRNA levels by reverse transcriptase‐polymerase chain reaction, or supernatants were collected after 48 h for determination of cytokine production by enzyme‐linked immunosorbent assay (ELISA). Morphine enhanced mRNA expression of interleukin (IL)‐12 p40 and tumor necrosis factor α (TNF‐α) compared with controls, whereas IL‐10 levels were unchanged by drug treatment. ELISA data showed that both IL‐12 p40 and p70 were increased by morphine. The enhancement of IL‐12 at both the mRNA and protein levels was antagonized by naltrexone, indicating that the modulation of this cytokine by morphine is via a classic opioid receptor. These results are particularly interesting in light of our previous observation that 48 h after morphine pellet implantation, the peritoneal cavity is colonized with gram‐negative and other enteric bacteria. The enhancement of IL‐12 by morphine might be related to morphine‐induced sepsis.