In addition to these proinflammatory functions, the prolonged stimulation of cells with S100A8 and S100A9 can induce hypo-responsiveness in monocytes and macrophages similar to the well-known endotoxin tolerance and thereby subsequently trigger immune paralysis, which is the major risk factor for enhanced morbidity and mortality during sepsis and SIRS (systemic inflammatory response syndrome) [29]. Here, S100A8 is linked to systemic inflammatory response syndrome.