Rosenberger Peter, Mühlbauer Eckhard, Weissmüller Thomas, Rommelspacher Hans, Sinha Pranav, Wernecke Klaus D, Finckh Ulrich, Rettig Jordan, Kox Wolfgang J, Spies Claudia D
Department of Anesthesiology and Intensive Care, University Hospital Charité, Humboldt-University of Berlin, Germany.
Alcohol Clin Exp Res. 2003 Nov;27(11):1693-700. doi: 10.1097/01.ALC.0000095636.44770.55.
Alcohol abuse may involve an altered neuroendocrine response that mediates lymphocyte-derived proopiomelanocortin (POMC) production and inflammation. We investigated POMC messenger RNA (mRNA) expression in human lymphocytes ex vivo and their relation to plasma ACTH and immunoreactive beta-endorphin (IR-beta-EP) after intravenous injection of human corticotropin releasing factor (hCRF) in chronic alcoholics (n = 12) and nonalcoholics (n = 12) before surgery. Lipopolysaccharide-stimulated interleukin (IL)-1 receptor antagonist (IL-1 Ra) as a marker for chronic inflammation was determined.
Chronic alcohol abuse was diagnosed according to DSM-IV criteria and alcohol consumption >60 g/day. A reverse transcription-polymerase chain reaction method with total RNA and subsequent solid phase minisequencing was used to quantify lymphocytic POMC mRNA after intravenous hCRF injection. Plasma ACTH, cortisol, and lipopolysaccharide-stimulated IL-1 Ra of monocytes were measured by enzyme-linked immunosorbent assay, and plasma IR-beta-EP was measured by using radioimmunoassay.
Baseline values of POMC mRNA content in lymphocytes and IL-1 Ra of chronic alcoholics were significantly increased compared with nonalcoholics (p < 0.01). Thirty minutes after intravenous hCRF injection, a significant increase of lymphocytic POMC mRNA was measured (p < 0.05) in nonalcoholics, whereas in chronic alcoholics a significant decrease was observed (p < 0.05).
Chronic alcoholic patients had an altered neuroendocrine immune axis before intravenous hCRF administration and were not able to adjust to intravenous CRF injection by increasing lymphocytic POMC mRNA expression.
