Decreased proopiomelanocortin mRNA in lymphocytes of chronic alcoholics after intravenous human corticotropin releasing factor injection

Decreased proopiomelanocortin mRNA in lymphocytes of chronic alcoholics after intravenous human corticotropin releasing factor injection

Rosenberger P; Muhlbauer E; Weissmuller T; Rommelspacher H; Sinha P; Wernecke KD; Finckh U; Rettig J; Kox WJ; Spies CD

Alcoholism, Clinical And Experimental Research

2003

Female; Humans; Male; Adult; Aged; Middle Aged; Biomarkers of Pain; Nonparametric; Statistics; RNA; Corticotropin-Releasing Hormone/pharmacology; Alcoholism/blood/metabolism; Lymphocytes/drug effects/metabolism; Messenger/biosynthesis/genetics; Pro-Opiomelanocortin/biosynthesis/genetics

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

2003

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