Current trends in inflammatory and immunomodulatory mediators in sepsis

Sepsis refers to severe systemic inflammation in re-sponse to invading pathogens. An overwhelming im-mune response, as mediated by the release of various inflammatory mediators, can lead to shock, multiple or-gan damage, and even death. Cytokines, proteases, lipid mediators, gaseous substances, vasoactive pep-tides, and cell stress markers play key roles in sepsis pathophysiology. Various adhesion molecules and chemokines sequester and activate neutrophils into the target organs, further augmenting inflammation and tis-sue damage. Although the anti-inflammatory sub-stances counterbalance proinflammatory mediators, prolonged immune modulation may cause host suscep-tibility to concurrent infections, thus reflecting enor-mous challenge toward developing effective clinical therapy against sepsis. To understand the complex in-terplay between pro- and anti-inflammatory phenome-non in sepsis, there is still an unmet need to study newly characterized mediators. In addition, revealing the current trends of novel mediators will upgrade our understanding on their signal transduction, cross-talk, and synergistic and immunomodulating roles during sepsis. This review highlights the latest discoveries of the mediators in sepsis linking to innate and adaptive immune systems, which may lead to resolution of many unexplored queries. J. Leukoc. Biol. 93: 329–342