Morphine inhibits transcriptional activation of IL-2 in mouse thymocytes

Sabita Roy, Rebecca B. Chapin, Kelly J. Cain, Richard G. Charboneau, S. Ramakrishnan, Roderick A. Barke

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Chronic treatment of mice with morphine affects the proliferation, differentiation, and function of immune cells. In the present study, we investigated the mechanism by which morphine inhibits phytohemagglutinin (PHA)/interleukln-1 (IL-1)-induced thymocyte proliferation. When compared to control cultures, morphinetreated thymocytes showed decreased steady-state levels of bioactive IL-2 and IL-2 mRNA. The reduced IL-2 concentration and reduced transcript levels correlated well with a decreased rate of synthesis of IL-2 mRNA as determined by nuclear runoff assays. Subsequent studies showed that morphine treatment affected transcriptional control elements of the IL-2 promoter by inhibiting the synthesis of a specific trans-activating nuclear factor, c-Fos. c-Fos mRNA levels measured by semiquantitative RT-PCR were significantly decreased in thymocytes following treatment with morphine and activation with PHA and IL-1. Under identical conditions, c-Jun mRNA levels were not altered. Electrophoretic mobility shift studies with the AP- 1 consensus oligonucleotide showed significantly decreased levels of AP-1- protein complex formation in nuclear extracts prepared from morphine-treated cells. These studies demonstrate for the first time that opioid alkaloids such as morphine can impair mitogen-lymphokine-activated thymocyte proliferation by interfering with transcriptional activation of the IL-2 gene.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalCellular Immunology
Issue number1
StatePublished - Jul 10 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology


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