TY - JOUR
T1 - A murine model of persistent inflammation, immune suppression, and catabolism syndrome
AU - Pugh, Amanda M.
AU - Auteri, Nicholas J.
AU - Goetzman, Holly S.
AU - Caldwell, Charles C.
AU - Nomellini, Vanessa
N1 - Funding Information:
The authors would like to thank Lisa England for her assistance with the surgeries and tissue collection. The work was funded in part by the National Institute of Health Grant T32 GM08478. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2017/8/10
Y1 - 2017/8/10
N2 - Critically ill patients that survive sepsis can develop a Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS), which often leads to extended recovery periods and multiple complications. Here, we utilized a cecal ligation and puncture (CLP) method in mice with the goal of creating a model that concurrently displays all the characteristics of PICS. We observed that, after eight days, mice that survive the CLP develop persistent inflammation with significant myelopoiesis in the bone marrow and spleen. These mice also demonstrate ongoing immune suppression, as evidenced by the decreased total and naïve splenic CD4 and CD8 T cells with a concomitant increase in immature myeloid cells. The mice further display significant weight loss and decreased muscle mass, indicating a state of ongoing catabolism. When PICS mice are challenged with intranasal Pseudomonas aeruginosa, mortality is significantly elevated compared to sham mice. This mortality difference is associated with increased bacterial loads in the lung, as well as impaired neutrophil migration and neutrophil dysfunction in the PICS mice. Altogether, we have created a sepsis model that concurrently exhibits PICS characteristics. We postulate that this will help determine the mechanisms underlying PICS and identify potential therapeutic targets to improve outcomes for this patient population.
AB - Critically ill patients that survive sepsis can develop a Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS), which often leads to extended recovery periods and multiple complications. Here, we utilized a cecal ligation and puncture (CLP) method in mice with the goal of creating a model that concurrently displays all the characteristics of PICS. We observed that, after eight days, mice that survive the CLP develop persistent inflammation with significant myelopoiesis in the bone marrow and spleen. These mice also demonstrate ongoing immune suppression, as evidenced by the decreased total and naïve splenic CD4 and CD8 T cells with a concomitant increase in immature myeloid cells. The mice further display significant weight loss and decreased muscle mass, indicating a state of ongoing catabolism. When PICS mice are challenged with intranasal Pseudomonas aeruginosa, mortality is significantly elevated compared to sham mice. This mortality difference is associated with increased bacterial loads in the lung, as well as impaired neutrophil migration and neutrophil dysfunction in the PICS mice. Altogether, we have created a sepsis model that concurrently exhibits PICS characteristics. We postulate that this will help determine the mechanisms underlying PICS and identify potential therapeutic targets to improve outcomes for this patient population.
KW - Chronic critical illness
KW - PICS
KW - Sepsis
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U2 - 10.3390/ijms18081741
DO - 10.3390/ijms18081741
M3 - Article
C2 - 28796194
AN - SCOPUS:85027199333
SN - 1661-6596
VL - 18
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 8
M1 - 1741
ER -