While it was thought initially that HMGB1 was released only from cells of the immune system, other cells have since been demonstrated to actively secrete alarmins. The first non-immune cell to be studied for active HMGB1 secretion was the pituicyte, which was found to release HMGB1 in response to IL-1 or TNFα stimulation (41) . Enterocytes release HMGB1 following stimulation with a cytokine mixture (42) . Hepatocytes also can release HMGB1 in response to hypoxic conditions or oxida-tive stress; this release appears to be mediated by calcium signaling changes within the cell (43) .