By applying this approach to CS/CPB-induced genes in peripheral blood, we identified a gene-regulatory network connecting the signals mediated by exposure of circulating blood cells to ischemia and reperfusion in heart, lungs as well as distant organs (e.g. HIF1apha) or priming of leukocytes via the extracorporeal CPB circuit (e.g. TLR4) with signals that execute and facilitate the systemic inflammatory response (e.g. IL-6 or MMP9). The gene discussed is TLR4; the disease is ischemia.