Methionine-enkephalin stimulates interleukin-6 mRNA expression:: Human plasma levels in coronary artery bypass grafting

Abstract

Opioid peptides have the ability to regulate immunocompetent cells. The present study extends this phenomenon to include an interaction with interleukin (IL)-6. We demonstrate that methionine-enkephalin (met-enkephalin) stimulates IL-6 mRNA expression in mice as determined by RNA isolation and hybridization with IL-6 cDNA. In mice, met-enkephalin [0.1 and 1 mg/kg intraperitoneal exposure for 6 days] also enhanced serum IL-6 levels. The in vivo data demonstrate that met-enkephalin upregulates IL-6 levels via an increase in transcriptional activity. Further, pre- and postoperative IL-6 and met-enkephalin levels were determined in the plasma of seven patients. First an increase in met-enkephalin plasma levels occurred (8.9±2.9 to 135±18 pg/ml; P<0.005), and then an increase in plasma IL-6 levels (2.1±1.5 to 237±50 pg/ml; P<0.001), suggesting that, as in mice, met-enkephalin induces IL-6 production. Taken together, the data strongly suggest that opioid peptides may be important as one of the chemical signaling molecules initiating the diffuse inflammatory response associated with coronary artery bypass grafting.