Intoxication- and Withdrawal-Dependent Expression of Central and Peripheral Cytokines Following Initial Ethanol Exposure
Article first published online: 22 AUG 2014
Copyright © 2014 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 38, Issue 8, pages 2186–2198, August 2014
How to Cite
Doremus-Fitzwater, T. L., Buck, H. M., Bordner, K., Richey, L., Jones, M. E. and Deak, T. (2014), Intoxication- and Withdrawal-Dependent Expression of Central and Peripheral Cytokines Following Initial Ethanol Exposure. Alcoholism: Clinical and Experimental Research, 38: 2186–2198. doi: 10.1111/acer.12481
- Issue published online: 22 AUG 2014
- Article first published online: 22 AUG 2014
- Manuscript Accepted: 21 APR 2014
- Manuscript Received: 11 SEP 2013
- NIH. Grant Number: R21AA016305-01
- the Developmental Exposure Alcohol Research Center (DEARC. Grant Number: P50AA017823
- the Center for Development and Behavioral Neuroscience at Binghamton University
Evidence has emerged demonstrating that ethanol (EtOH) influences cytokine expression within the central nervous system, although most studies have examined long-term exposure. Thus, the cytokine response to an acute EtOH challenge was investigated, in order to characterize profiles of cytokine changes following acute exposure.
Rats pups were injected intraperitoneally (i.p.) with 2-g/kg EtOH, and IL-1 mRNA and protein were assessed 0, 60, 120, 180, and 240 minutes post injection (Experiment 1). In Experiments 2 to 5, the expression of several cytokines was examined in adult male rats during acute intoxication (3 hours after 4-g/kg EtOH), as well as withdrawal (18 hours post injection), after i.p. or intragastric (i.g.) EtOH administration.
Early in ontogeny, acute EtOH significantly decreased brain IL-1 mRNA and protein. Subsequently, when adult rats were examined, significant and temporally dynamic alterations in central and peripheral cytokines were observed following acute i.p. EtOH exposure (4 g/kg). Although cytokine- and region-dependent central IL-6 expression was generally increased and tumor necrosis factor alpha decreased during intoxication, IL-1 expression exhibited increases during withdrawal. In the periphery, acute i.p. EtOH elevated expression of all cytokines, with the response growing in magnitude as the time post injection increased. Following acute i.g. EtOH (4 g/kg), intoxication-related increases in IL-6 expression were again observed in the paraventricular nucleus of the hypothalamus (PVN), although to a lesser extent. Long-term, voluntary, intermittent EtOH consumption resulted in tolerance to the effects of an i.g. EtOH challenge (4 g/kg) on PVN IL-6 expression, whereas these same elevations in IL-6 expression were still seen in the amygdala in rats with a history of moderate EtOH intake. Treatment with minocycline did not significantly attenuate i.p. or i.g. EtOH-induced changes in central cytokine expression.
Together, these studies provide a foundation for understanding fluctuations in central and peripheral cytokines following acute EtOH as potential contributors to the constellation of neural and behavioral alterations observed during EtOH intoxication and withdrawal.