Introduction: The mechanisms behind the detrimental effects of ethanol on the liver remain uncertain. It has been suggested that the presence of ethanol in the gut lumen promotes a ’leaky gut’ allowing bacterial products to translocate to the bloodstream causing an inflammatory response. Furthermore, the ethanol-induced hormone fibroblast growth factor 21 (FGF-21) has emerged as a potential safeguard from ethanol-induced liver injury. Here, we aimed to investigate how ethanol administered intragastrically and intravenously, respectively, influences circulating markers of inflammation and FGF-21.

Materials and Method: In a double-blinded, randomized cross-over design, we subjected 12 fasted healthy men (age 25.3±3.9 years; body mass index (BMI) 22.6±2.6 kg/m2 (mean±SD)) to intragastrically instilled ethanol (0.70 g ethanol per kg body weight in a 20% (v/w) solution infused over 5 minutes) and isoethanolaemic iv ethanol infusion, respectively, on two separate experimental days, and evaluated a range of circulating markers of inflammation and liver function as well as FGF-21.

Results: No increment in plasma sCD163, or any other inflammation markers (lipopolysaccharide binding protein, tumor necrosis factor-α, interferon-γ, interleukin-10 (IL), IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-6, and IL-8), was observed. Plasma FGF-21 levels increased significantly (nine times baseline level), similarly and throughout both experimental days.

Conclusion: Neither ’oral’ nor iv ethanol elicited significant changes in circulating markers of macrophage activation or inflammation, but increased plasma FGF-21 significantly regardless of the administration form suggesting a direct ethanol effect on FGF-21 secretion.