REM sleep is essential for maintenance of body physiology and its deprivation is fatal. We observed that the levels of ALT and AST enzymes and pro-inflammatory cytokines like IL-1 beta, IL-6 and IL-12 circulating in the blood of REM sleep deprived rats increased in proportion to the extent of sleep loss. But in contrast the levels of IFN-gamma and a similar to 200 kDa protein, identified by N-terminal sequencing to be alpha-1-inhibitor-3(A1I3), decreased significantly. Quantitative PCR analysis confirmed that REM sleep deprivation down regulates AII3 gene and up regulates IL1 beta, IL6 and their respective receptors gene expression in the liver initiating its inflammation. (C) 2011 Elsevier Inc. All rights reserved.