BACKGROUND: Acute ethanol administration just prior to a stimulus, such as the viral mimic poly I:C, results in decreased proinflammatory cytokine production. Studies have indicated that this suppression is not primarily mediated by glucocorticoids (corticosterone in mice) released in the ethanol-induced stress response. Fewer studies have been done on the effects of acute ethanol administration 12 or more hours prior to a stimulus. The purpose of this study was to determine the role of corticosterone on these effects. Also, since gender differences occur in immune responses, separate experiments were performed using male and female mice. METHODS: Mice were treated with ethanol 15 min or 12h before stimulation by poly I:C to demonstrate immunosuppressive effects of ethanol on cytokine production. A glucocorticoid synthesis inhibitor was used to manipulate corticosterone levels. RESULTS: Short-term and persistent effects of acute ethanol exposure on corticosterone and cytokine levels were nearly identical in males and females. Blocking glucocorticoid synthesis altered the inhibition of some cytokines, particularly IL-6, in females, but not in males. CONCLUSION: These results indicate that the short-term effects of acute ethanol on poly I:C-induced cytokine production are not primarily mediated by corticosterone in male or female mice. In female mice, however, corticosterone does appear to mediate the persistent effects of acute ethanol administration on poly I:C- induced IL-6 levels. Since many IL-6 related disorders are gender associated, further research into the bidirectional effects of the HPG and HPA axes on alterations in cytokine production mediated by ethanol is warranted.
BACKGROUND: Acute ethanol administration just prior to a stimulus, such as the viral mimic poly I:C, results in decreased proinflammatory cytokine production. Studies have indicated that this suppression is not primarily mediated by glucocorticoids (corticosterone in mice) released in the ethanol-induced stress response. Fewer studies have been done on the effects of acute ethanol administration 12 or more hours prior to a stimulus. The purpose of this study was to determine the role of corticosterone on these effects. Also, since gender differences occur in immune responses, separate experiments were performed using male and female mice. METHODS:Mice were treated with ethanol 15 min or 12h before stimulation by poly I:C to demonstrate immunosuppressive effects of ethanol on cytokine production. A glucocorticoid synthesis inhibitor was used to manipulate corticosterone levels. RESULTS: Short-term and persistent effects of acute ethanol exposure on corticosterone and cytokine levels were nearly identical in males and females. Blocking glucocorticoid synthesis altered the inhibition of some cytokines, particularly IL-6, in females, but not in males. CONCLUSION: These results indicate that the short-term effects of acute ethanol on poly I:C-induced cytokine production are not primarily mediated by corticosterone in male or female mice. In female mice, however, corticosterone does appear to mediate the persistent effects of acute ethanol administration on poly I:C- induced IL-6 levels. Since many IL-6 related disorders are gender associated, further research into the bidirectional effects of the HPG and HPA axes on alterations in cytokine production mediated by ethanol is warranted.
Authors: Ashley M Geiger; Kenneth P Pitts; Joachim Feldkamp; Clemens Kirschbaum; Jutta M Wolf Journal: Brain Behav Immun Date: 2015-07-14 Impact factor: 7.217