Further evidence for innate immunity in alcohol abuse and dependence comes from human genetic association and linkage studies. For example, human studies found a link between NFKB1 [43] and TNF [44,45] polymorphisms and alcohol abuse. Genetic linkage of the IL-1 and IL-1 receptor antagonist genes to alcoholism has also been reported [46,47]. In addition, CYP2E1, a gene involved in alcohol metabolism, is associated with risk of alcoholism [48]. CYP2E1 leads to increased expression of reactive oxygen species and propagation of inflammatory NF-κB responses in liver Kupffer cells [49]. Collectively, an array of molecular, behavioral, and genomic studies substantiate a prominent role for the innate immune system in the neurobiology of alcohol action.
