Alcoholism: Sleep and Cytokines
Michael Irwin, Principal Investigator

Disturbances of sleep are prominent in alcoholic patients, persist into recovery, and have recently been found to predict those alcoholics who are most likely to relapse. This study hypothesizes that the complex cytokine network is one system that is associated with declines of sleep depth and loss of delta sleep in alcoholics. Basic observations demonstrate that pro-inflammatory and helper T cell type 1/type 2 (Th1/Th2) cytokines have a physiological role in the regulation of sleep with both somnogenic and inhibitory effects depending on the cytokine, dose, and circadian phase. However, translation of these basic mechanisms into the clinical setting is limited, and virtually no study has examined the relationships between cytokine expression and disordered sleep in patients with chronic alcohol dependence. Because evidence further indicates that African American alcoholics are at increased risk for infectious disease morbidity, disordered sleep, and abnormal cytokine expression, this study further proposes to examine the effects of alcohol dependence on sleep and on the relationships between sleep and pro-inflammatory and Th1/Th2 cytokine expression in "at risk" African American alcoholics vs. Euro-American alcoholics and controls. Sleep deprivation serves as a naturalistic probe of sleep regulatory processes to evaluate the capacity of sleep recovery in alcoholics and to test the effects of sleep on immune system functioning. The specific aims of this study are to: 1) evaluate whether alcohol dependence and African American ethnicity are associated with disturbances of sleep including loss of delta sleep and deficits in recovery of delta sleep following sleep deprivation as compared to ethnicity matched controls; 2) establish the impact of sleep on the diurnal- and nocturnal expression of pro-inflammatory-, Th1, and Th2 cytokine levels in African American- and Euro-American alcoholics vs. controls; 3) determine the predictive validity of circulating interlekin-6 on delta sleep. This study will advance our understanding of the reciprocal relationships between cytokines and sleep in alcohol dependence with implications for answering why sleep is disordered in alcoholics patients and for the development of novel treatments (e.g., cytokine antagonists) for sleep disturbance in alcoholism