Mu opioid receptor agonist-selective regulation of interleukin-4 in T lymphocytes

• Opioids produce immunomodulatory effects, among these is the induction of IL-4.
• Morphine and buprenorphine produce an approximately 10 fold induction of IL-4 mRNA.
• Methadone, fentanyl, beta-endorphin and loperamide induce IL-4 about 60 fold.
• Biased signaling at mu opioid receptors may explain this observation.

Opioids are irreplaceable for the treatment of severe pain. However, opioid-induced immunomodulation affects therapies. Here we report that treatment of human T lymphocytes with the opioids fentanyl, methadone, loperamide and beta-endorphin resulted in a strong induction of the cytokine interleukin-4. In contrast, morphine and buprenorphine induced markedly and significantly lower levels of interleukin-4 mRNA and protein. These findings suggest agonist-biased μ opioid receptor signaling in T cells. In the future, better knowledge about agonist-specific immunomodulatory effects of opioids offers the possibility to select drugs for a therapy with more favorable and/or less detrimental side effects in immune cells.