Low concentrations of ethanol inhibits prolactin-induced mitogenesis and cytokine expression in cultured astrocytes.
Whereas the immunosuppressive effects of chronic alcohol use have been well documented, little is known about the effect of ethanol on the neuroimmune response. We previously demonstrated that PRL is a potent mitogen and induces the expression of several inflammatory cytokines, including tumor necrosis factor-alpha (TNF alpha) in cultured rat astrocytes. The aim of this study was to examine the effects of ethanol on PRL-induced mitogenesis and TNF alpha expression in cultured rat astrocytes. We found that low concentrations of ethanol blocked PRL-induced increases in [3H]thymidine incorporation and TNF alpha levels. In contrast, ethanol had no effect on platelet-derived growth factor- or fibroblast growth factor-induced increases in [3H]thymidine incorporation. Radioligand binding analysis revealed that ethanol did not effect PRL receptor binding. We also examined the effect of prenatal alcohol exposure (PAE) on PRL-induced mitogenesis and cytokine expression. PAE during the last 5 days of gestation blunted the PRL-induced increase in [3H]thymidine incorporation and TNF alpha levels in cells grown in the absence of ethanol in the culture medium. Addition of ethanol to primary PAE astrocyte cultures resulted in a modest increase in basal [3H]thymidine incorporation, but completely blocked the PRL-induced increase in [3H]thymidine incorporation and TNF alpha levels. In contrast, platelet-derived growth factor- and serum (10%)-induced increases in [3H]thymidine incorporation remained intact. Together, these data indicate that ethanol blocks PRL-induced mitogenesis and the expression of TNF alpha in cultured rat astrocytes and are consistent with the possible inhibition of the astrocytic response by ethanol in vivo.
DeVito
W J
WJ
Division of Endocrinology, University of Massachusetts Medical Center, Worcester 01655, USA.
Stone
S
S
Mori
K
K
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008938:Mitosis / Q000187:drug effects*; D009994:Osmolar Concentration; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D011388:Prolactin; D013936:Thymidine