SEP-12: APOSEC, A NOVEL IMMUNOMODULATORY SECRETOME THERAPEUTIC, IS INEFFECTIVE IN THE ACUTE PHASE OF SEVERE MOUSE CLP SEPSIS

INTRODUCTION:Septic deaths occur in a deranged environment featuring both hyperinflammatory and immunosuppressive responses. At present, there is no approved immune-modulatory drug able to restore this imbalance. This study aimed to test a newly developed blood cell secretome preparation (APOSEC) upon outcome in the acute mouse model of polymicrobial sepsis. METHODS:3-month-old female CD-1 mice (n = 40) underwent medium-severe cecal ligation and puncture (CLP) and were treated intraperitoneally with APOSEC (obtained from irradiated/apoptotic peripheral blood mononuclear cells) or saline at 6 h and 24 h post-CLP. We assessed 28-day survival, circulating organ function parameters and complete blood cell (CBC) counts with differential over 0h-96 h post-CLP. RESULTS:APOSEC treatment failed to exert any benefit in CLP either in the acute (days 1–5) or chronic (days 6–28) phase; 28-day survival was 30% in control and 25% in the APOSEC group. Control CLP caused a pronounced increase (peak at 24 h) of circulating LDH (to 1070 U/l), urea (to 118 U/l) and ALT (to 106 U/l) as well as decrease (nadir at 24 h) in blood glucose (to 43 mg/dl). APOSEC failed to ameliorate those changes; in fact, an opposite deteriorating trend (p > 0.05) was present for all parameters. In both groups, CBC analysis demonstrated an identical and severe post-CLP lymphopenia (and minimal neutropenia) with nadir at 48 h (0.6 K/μl). Similar was true for decrease in hemoglobin concentration and erythrocyte and platelet counts. CONCLUSION:This study demonstrated that deregulation of immuno-inflammatory responses and organ/cellular homeostasis caused by a relatively severe CLP insult was too rapid/strong to be effectively modified by APOSEC.