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Int. J. Mol. Sci. 2017, 18(8), 1741; doi:10.3390/ijms18081741

A Murine Model of Persistent Inflammation, Immune Suppression, and Catabolism Syndrome

1
Division of Research, Department of Surgery, University of Cincinnati, Cincinnati, OH 45229, USA
2
Division of Trauma, Critical Care, Acute Care Surgery, Department of Surgery, University of Cincinnati, Cincinnati, OH 45229, USA
*
Authors to whom correspondence should be addressed.
Received: 10 July 2017 / Revised: 2 August 2017 / Accepted: 7 August 2017 / Published: 10 August 2017
(This article belongs to the Special Issue Sepsis)
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Abstract

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. View Full-Text
Keywords: PICS; chronic critical illness; sepsis PICS; chronic critical illness; sepsis
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MDPI and ACS Style

Pugh, A.M.; Auteri, N.J.; Goetzman, H.S.; Caldwell, C.C.; Nomellini, V. A Murine Model of Persistent Inflammation, Immune Suppression, and Catabolism Syndrome. Int. J. Mol. Sci. 2017, 18, 1741.

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