IL-18 and Macrophage Activation Syndrome

Macrophage activation syndrome (MAS) is a type of systemic inflammatory response syndrome distinguished by high fever, cytopenias (low cell counts), liver dysfunction, clotting problems, extremely high levels of ferritin, and often hemophagocytosis (macrophages that have consumed other blood cells). Though rheumatologists grapple with MAS as a complication of some rheumatic diseases, MAS-like physiology is seen in other contexts, such as viral and bacterial infection, cancer and transplantation.

One feature that seems to define MAS is extraordinary elevation of the cytokine Interleukin-18 (IL-18). IL-18 requires an inflammasome for its activation, but until recently it was unclear whether IL-18 was helping drive MAS or was just an epiphenomenon. We recently discovered an association between the NLRC4 inflammasome, extraordinary IL-18, and MAS. We are actively working to fill in the mechanistic gaps.

A murine splenic hemophagocyte.

A murine splenic hemophagocyte.

Increased proliferation of intestinal epithelial cells in NLRC4 gain-of-function mice.

Increased proliferation of intestinal epithelial cells in NLRC4 gain-of-function mice.