Figure 6.

Schematic diagram showing the role of S100A8 in the prevention of cytokine storm during endotoxemia in lean subjects, and patients with obesity and diabetes

In lean subjects, adaptive induction of S100A8 in myelomonocytic cells through TLR4-mediated signaling during endotoxemia attenuates the excessive production of inflammatory cytokines and prevents lethal endotoxemia. In people with obesity and diabetes, the insufficient induction of S100A8 by endotoxemia, possibly due to chronic low-grade inflammation, fails to suppress the chain reaction of inflammatory cytokine production and results in cytokine storm and increased mortality. Exogenous supplementation with S100A8 may be able to prevent death in patients with obesity and diabetes during sepsis.