Precision medicine for sepsis —Focusing on disseminated intravascular coagulation （DIC） and immunoparalysis—

Abstract

It has been widely recognized that sepsis causes hypercytokinemia in the acute phase, needing to be abated as soon as possible. On the other hand, we reported that critically ill patients with extreme hypercytokinemia or with sky-high interleukin （IL）-6 blood levels show some specific genotypic distributions on upstream cytokine genes, e.g., TNF promoter single nucleotide polymorphism （SNP） and IL1RA variable number of tandem repeat （VNTR）. Thus, SIRS（systemic inflammatory response syndrome）was thought to precede CARS（compensatory anti-inflammatory response syndrome）, but recently, both are found to occur concurrently after the septic insult. CARS, or immunoparalysis, is one of the harmful host responses that is more challenging to address than SIRS. Precision immunotherapy garners attention as a counter-measure against the pathophysiology. Inhibitory receptors such as PD-1 and CTLA-4, immune checkpoint inhibitors, are representative compounds for immune-enhancing therapy. A PD1 SNP （rs11568821） was reported to be associated with the 90-day mortality in sepsis. Also, the two SNPs on anti-apoptotic BCL2 are related to the incidence rate of acute kidney injury secondary to infection. The recent randomized control trial for sepsis （SCARLET） is designed to target a specific patient cohort with coagulopathy and organ dysfunctions, meaning precision medicine. Intensivists should place emphasis on measures taking the genetic conditions of critically ill patients into consideration in the future.