Primed circulating monocytes are a source of IL-1β in patients with cirrhosis and ascites.

We read with great interest the study of Monteiro and colleagues1 reporting the diagnostic significance and the prognostic relevance of elevated serum concentrations of interleukin (IL)-1α in compensated cirrhosis and IL-1β in recompensated cirrhosis. While we do agree that systemic inflammation is a major driver for the progression of liver disease and acute-on-chronic liver failure, caution is advised when interpreting serum IL-1β concentrations as evidence for underlying inflammasome activation causing complications of cirrhosis. Studies1–4 have been inconsistent about stage-dependent concentrations of circulating IL-1β in cirrhosis and acute-on-chronic liver failure (ACLF). Although some of these discrepancies can be attributed to differences in patients, cohort sizes, causes and severity of liver damage, the short serum half-life of cleaved IL-1β, and the sensitivity and specificity of the assays used, one major factor presumably affecting serum concentration is the cellular source of IL-1β and its mode of release. The release of bioactive IL-1β from murine macrophages has first been described as a two-step activation dogma. While a first (priming) signal would be provided by pathogen-associated molecular patterns (PAMPs) or inflammatory cytokines in order to upregulate the inflammasome components, a second signal would …