Research
Early down-regulation of the pro-inflammatory potential of monocytes is correlated to organ dysfunction in patients after severe multiple injury: a cohort study
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* Corresponding author: Chlodwig Kirchhoff chlodwig.kirchhoff@mac.com
1 Department of Orthopaedic Surgery and Traumatology, Klinikum Rechts der Isar, Technische Universitaet, Ismaningerstrasse 22, 81675 Munich, Germany
2 Department of Orthopaedic Surgery and Traumatology, Campus Innenstadt, Ludwig-Maximilians Universitaet, Nussbaumstrasse 20, 80336 Munich, Germany
3 Department of Surgery, Campus Grosshadern, Ludwig-Maximilians Universitaet, Munich, Germany, Marchioninistrasse 15, 81377 Munich, Germany
4 Department of Clinical Chemistry and Clinical Biochemistry, Campus Innenstadt, Ludwig-Maximilians Universitaet, Nussbaumstrasse 20, 80336 Munich, Germany
Critical Care 2009, 13:R88 doi:10.1186/cc7914
Published: 11 June 2009Abstract
Introduction
Severe tissue trauma results in a general inflammatory immune response (SIRS) representing an overall inflammatory reaction of the immune system. However, there is little known about the functional alterations of monocytes in the early posttraumatic phase, characterized by the battle of the individual with the initial trauma.
Methods
Thirteen patients with severe multiple injury; injury severity score (ISS) >16 points (17 to 57) were included. The cytokine synthesis profiles of monocytes were characterized on admission, and followed up 6, 12, 24, 48, and 72 hours after severe multiple injury using flow cytometry. Whole blood was challenged with lipopolysaccharide (LPS) and subsequently analyzed for intracellular monocyte-related TNF-α, IL-1β, IL-6, and IL-8. The degree of organ dysfunction was assessed using the multiple organ dysfunction syndrome (MODS)-score of Marshall on admission, 24 hours and 72 hours after injury.
Results
Our data clearly show that the capacity of circulating monocytes to produce these mediators de novo was significantly diminished very early reaching a nadir 24 hours after severe injury followed by a rapid and nearly complete recovery another 48 hours later compared with admission and controls, respectively. In contrast to the initial injury severity, there was a significant correlation detectable between the clinical signs of multiple organ dysfunction and the ex vivo cytokine response.
Conclusions
As our data derived from very narrow intervals of measurements, they might contribute to a more detailed understanding of the early immune alterations recognized after severe trauma. It can be concluded that indeed as previously postulated an immediate hyperactivation of circulating monocytes is rapidly followed by a substantial paralysis of cell function. Moreover, our findings clearly demonstrate that the restricted capacity of monocytes to produce proinflammatory cytokines after severe injury is not only an in vitro phenomenon but also undistinguishable associated with the onset of organ dysfunction in the clinical scenario.