Nerve growth factor produced by activated human monocytes/macrophages is severely affected by ethanol.
Ethanol intake impairs immune function and increases the incidence of infection in the host. Although the precise cellular target of this immunotoxic action is still unknown, findings of several studies have shown that ethanol acts on the immune response predominantly by interfering with the ability of blood monocyte-derived macrophages to produce cytokines and growth factors. Nerve growth factor (NGF) represents a key molecule in monocyte/macrophage-mediated responses. Thus, we tested the hypothesis that exposure to ethanol would affect NGF synthesis as well as expression of NGF receptor trkA in this cell population. Because NGF has been reported to affect the synthesis of proinflammatory cytokines, we also evaluated whether the production of tumor necrosis factor-alpha would be affected by ethanol-mediated changes in NGF synthesis. The study results demonstrated that the acute exposure of lipopolysaccharide-activated human monocyte/macrophage cultures to ethanol led to a sharp decrease in endogenous-produced NGF, which is associated with a reduced expression of high-affinity NGF receptor on cell membrane, and to a concomitant impairment of tumor necrosis factor-alpha production. Taken together, the current findings support the suggestion that a new mechanism exists by which ethanol can compromise the efficiency of the mononuclear phagocyte system in dealing with infection and host inflammatory response.
Caroleo
Maria Cristina
MC
Department of Pharmacobiology, Faculty of Pharmacy, University of Calabria, 87036 Cosenza, Italy.
Costa
Nicola
N
Tirassa
Paola
P
Aloe
Luigi
L
D002478:Cells, Cultured; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics
D000431:Ethanol; D020932:Nerve Growth Factor