The damage‐associated molecular pattern HMGB1 is elevated in human alcoholic hepatitis, but does not seem to be a primary driver of inflammation

The role of sterile inflammation caused by release of damage‐associated molecular patterns ( DAMP ) remains unclear in human alcoholic hepatitis ( AH ). The DAMP , high mobility group box‐1 protein ( HMGB 1) is released by tissue damage and inflammation. We aimed to investigate whether HMGB 1 is a primary inflammatory driver in AH by determining HMGB 1 serum levels and effects on inflammatory cells from AH patients. We measured serum HMGB 1 in 34 AH patients and 10 healthy controls using ELISA . Toll‐like receptor 4 ( TLR 4) and CD 14 expressions were assessed by flow cytometry on HMGB 1‐stimulated peripheral blood mononuclear cells ( PBMC ) and ELISA was used to measure TNF ‐α and IL ‐1β in the supernatants. We observed 5‐fold higher serum levels of HMGB 1 in AH patients at the day of diagnosis and day 30, but no associations to clinical outcome. HMGB 1 stimulation increased the expression of TLR 4 on CD 14+‐monocytes compared with unstimulated cells in the AH patients. The TNF ‐α and IL ‐1β production in response to HMGB 1 was diminished in AH patients. In conclusion, AH patients have increased levels of HMGB 1 in their blood. This combined with an increased TLR 4 expression, but an unaffected cytokine response to HMGB 1 suggest that HMGB 1 is not the primary driver of inflammation in AH .