Among the factors that induce the strong immune activation caused by alcohol abuse are: (1) a TLR4 direct agonism; (2) the upregulation of plasma LPS, which is also a TLR4 agonist; and (3) the overproduction of DAMPS such as HMGB1, which magnifies TLR4 activation (Figure 1). Here, HMGB1 is linked to alcohol abuse.