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(Journal of Leukocyte Biology. 2000;68:723-728.)
© 2000 by Society for Leukocyte Biology

Morphine enhances interleukin-12 and the production of other pro-inflammatory cytokines in mouse peritoneal macrophages

Xiaohui Peng, David M. Mosser, Martin W. Adler*,{dagger}, Thomas J. Rogers{dagger}, Joseph J. Meissler, Jr{dagger} and Toby K. Eisenstein{dagger}

Departments of Microbiology and Immunology,
* Pharmacology, and Center for Substance Abuse Research,
{dagger} Temple University School of Medicine, Philadelphia, Pennsylvania

Correspondence: Toby K. Eisenstein, Ph.D., Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140. E-mail: tke{at}astro.ocis.temple.edu

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-{gamma} (IFN-{gamma}: 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 {alpha} (TNF-{alpha}) 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.

Key Words: interleukin-10 • interferon-{gamma} • naltrexone




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