METHIONINE-ENKEPHALIN STIMULATES INTERLEUKIN-6 MESSENGER-RNA EXPRESSION - HUMAN PLASMA-LEVELS IN CORONARY-ARTERY BYPASS-GRAFTING

Opioid peptides have the ability to regulate immunocompetent cells. Th e present study extends this phenomenon to include an interaction with interleukin (IL)-6. We demonstrate that methionine-enkephalin (met-en kephalin) stimulates IL-6 mRNA expression in mice as determined by RNA isolation and hybridization with IL-6 cDNA, Ln mice, met-enkephalin [ 0.1 and 1 mg/kg intraperitoneal exposure for 6 days] also enhanced ser um IL-6 levels. The in vivo data demonstrate that met-enkephalin upreg ulates IL-6 levels via an increase in transcriptional activity. Furthe r, pre- and postoperative IL-6 and met-enkephalin levels were determin ed in the plasma of seven patients. First an increase in met-enkephali n plasma levels occurred (8.9 +/- 2.9 to 135 +/- 18 pg/ml; P<0.005), a nd then an increase in plasma IL-6 levels (2.1 +/- 1.5 to 237 +/- 50 p g/ml; P<0.001), suggesting that, as in mice, met-enkephalin induces IL -6 production. Taken together, the data strongly suggest that opioid p eptides may be important as one of the chemical signaling molecules in itiating the diffuse inflammatory response associated with coronary ar tery bypass grafting. (C) 1998 Elsevier Science Ireland Ltd.