It is well-known that ethanol metabolism mainly by ALD and CYP2E1 enzymes increases oxidative stress (OS) which is considered the primary mechanism of liver injury during ALD progression [3]. (A) Image shows basal status of OS, FLII, NXN, MYD88, and FLII/NXN/MYD88 complex in unexposed cells to ethanol effects. (B) Upon chronic ethanol exposition, OS levels increase and oxidize NXN disrupting FLII/NXN/MYD88 complex, and increasing FLII levels and secretion into the blood circulation. The complex might be differentially disrupted and MYD88 might increase its interaction with TLR4. Additionally, LPS administration partially reverts the effects of ethanol but NXN overexpression modifies the response of FLII/NXN/MYD88 complex to ethanol and/or LPS effects in vitro. The reversal effect of LPS might be due to the development of hepatic tolerance to neutralize the hyperactivation of TLR4/MYD88 signaling pathway.