Abstract
Polymorphonuclear leukocytes (PMNL) play important roles both in host defenses and systemic inflammatory responses after severe insults. The two-hit theory specifies that initial injury primes the inflammatory system, in particular PMNL and endothelium, and that exposure to a second stimulus induces an exaggerated inflammatory response and further tissue injury. These concepts have been introduced in animal studies and have not been proved in patients following severe insults. We evaluated the systemic inflammatory response to second hits in severe trauma patients based on the functions in PMNL, and reviewed the second hit phenomenon following severe injuries. Infections as second hits further enhanced the priming of PMNL in severely injured patients, but second hit priming in PMNL did not cause systemic vascular endothelial damage. Brain deaths after severe head injuries enhanced the priming of PMNL, and induced endothelial activation and organ damage. Secondary operations following trauma suppressed the oxidative activity in primed PMNL or inhibited the phagocytosis in non-primed PMNL, but the dynamic changes in PMNL functions did not cause further tissue injury or immunosuppression. These results suggest that the impacts of second hits on PMNL functions depend on the pre-operative priming conditions and the type of secondary insult. The concepts of two-hit theory may not be true in most cases and second hit phenomenon may be limited in trauma patients.
