V. Nomellini1, A. M. Pugh1, N. J. Auteri1, H. S. Goetzman1, C. C. Caldwell1 1University Of Cincinnati,Surgery,Cincinnati, OH, USA
Introduction: Advancements in the management of sepsis have improved overall mortality, particularly in the acute phases of the disease. However, those that survive often have prolonged and complicated recovery periods. In the later stages of sepsis, patients frequently exhibit a Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS), which is associated with prolonged hospitalizations, multiple complications, poor wound healing, profound disability, and long-term neurocognitive deficits.
Methods: Our lab has developed a murine model of PICS utilizing a cecal ligation and puncture (CLP) method. Male CF-1 mice underwent 33% cecal ligation with a single 25-gauge needle puncture. Mice that survived 8 days after CLP demonstrated the signature characteristics of PICS. This model generates a mortality rate of about 25%, emulating that of humans.
Results:We observed that, mice that survive the CLP develop persistent inflammation with significant myelopoiesis in the blood, bone marrow, and spleen eight days after the initial insult. These mice also demonstrate ongoing immune suppression, marked by decreased total and naïve splenic CD4 and CD8 T cells with an increase in immature myeloid cells. The mice further display significant weight loss, decreased thigh muscle mass, and perform significantly worse on the Rotarod test of coordination, indicating a state of ongoing catabolism. When PICS mice are challenged with Pseudomonas aeruginosa intranasally, mortality is significantly increased and bacterial clearance in the lungs is compromised.
Conclusion: Altogether, we have created a sepsis model that concurrently exhibits all the characteristics of PICS and confirms their susceptibility to a secondary bacterial challenge. Future studies involving this mouse model will examine the mechanisms underlying PICS in order to identify these patients early in their clinical course and develop potential therapeutic targets to improve outcomes for this patient population.