The Role Of PD-1/PD-L1Pathway In Acute Septic Peritonitis

OBJECTIVE: Sepsis represents a clinical syndrome resulting from the systemicinflammatory response to bacterial infection. The complicated proceeding ofpathophysiology in immune system of sepsis remains unclear, and it is difficult toadvance treatment of this important and frequent problem. The purpose of this studyis:(1) To establish a constant infectious abdominal peritonitis model in mice whichmimics the process of acute intestinal fistula in patients.(2) To set up a realtivelyindicator which could be early prognostic of mortality in severe septic animal models.(3) To reveal the expressions of different activated cell markers on immune cells inseptic mice adjusted to different stages of sepsis and reveal the function of innate oradaptive immune system which could have the key role in sepsis.METHODS:1) To establish a colon ascendens stent peritonitis model in mice.2) Toestablish early predictor of outcome in septic mice according to their temperature andjudge the septic condition (spesis or severe sepsis/septic shock) by septic parameters.3) To detect the change in immune cells according to the level of activator expressionfrom mice's peripheral blood, spleen and peritoneal fluid by the FACS Calibur FlowCytometer. To compare the expression of PD-1/PD-L1(CD274~+/CD279~+) in CD4~+Tlymphocytes in septic condition.RESULTS:1) The survival rate of CASP model was34.3%and major death eventsoccured in the early phase of septic condition. The CASP model could closely mimicthe relevant septic diffuse peritonitis.2) The mild hypothermia group (sepsis) had asignificantly higher survival rate (75%) than sereve hypothermia group (severesepsis/septic shock)(survival rate=0%, P<0.05). The septic parameters were moreserious in sereve hypothermia group (<32°C) comparing to the mild hypothermia (>32°C) group.3) The proportion of immune T cells in.peripheral blood and spleenwas increased in severe group. The expression of CD279was higher while CD274was lower in severe sepsis group. The expression of CD4~+CD25+T cell was higher insevere group rather than mild group. The expression of CD152,CD44,CD62L,CD40L,CD80had no differences. The macrophage in peritoneal cavity expressedhigh level of CD274in both mild and severe group.CONCLUSIONS:1) Establishment of a septic diffuse peritonitis model in mice.2)Temperature could be considered as early predictor in judging the lethal outcome inacute sepsis animal model;3) The dynamic change of expression in PD-1/PD-L1maycause the change in function of T lymphocytes in CASP mice, which lead to progressin severe sepsis/septic shock.