Inflammation plays a central role in the onset and progression of ALD. PPARγ ligands inhibited the pro-inflammatory behaviour of HSC downregulating the monocyte chemotactic protein-1 (MCP-1) [51]. Pioglitazone prevents liver injury by ethanol and LPS in rats [59, 60]. In this model, activation of PPARγ by pioglitazone was shown to reduce the production of TNFα by activated Kupffer cells. Kupffer cells are able to metabolize ethanol [61, 62] and chronic ethanol consumption induces CYP2E1 expression in Kupffer cells [63]. Although in acute alcohol induced-liver injury acetaldehyde has been shown to inhibit TNF-α release by Kupffer cells through inhibition of the NF-kB pathway [64, 65], in chronic alcohol abuse the role of Kupffer cell activation and TNF-α release in promoting liver injury is well established. It is therefore tempting to speculate that in ALD acetaldehyde, produced in Kupffer cells or hepatocytes, could lead to suppression of PPARγ transcriptional activity and promote the release of TNF-α. Indeed, enhanced release of TNF-α in response to acetaldehyde or LPS by Kupffer cells isolated from ethanol-fed rats has been reported [66, 67]. Moreover, in ALD
