Significant Decline of Peripheral Myeloid Dendritic Cells Following Multiple Trauma Dirk Henrich, Ph.D., 1 Marcus Maier, M.D., Borna Relja, M.Sc., Petar Trendafilov, Serin Schiessling, Manuela Wirth, Thorsten Ottilinger, Ann-Kathrin Nielsen, Hendrik Wyen, and Ingo Marzi, M.D. Department of Trauma Surgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany Submitted for publication February 4, 2008 Background. Dendritic cells (DC) represent an im- portant and integral part of the immune system and are potent initiators of inflammation. Two distinct subsets of DC have been identified: myeloid DC (MDC) and plasmacytoid DC (PDC), which differ widely in many respects. Despite the importance of the DC in the inflammatory response that occurs after severe multiple injury, there is a profound lack of informa- tion regarding the distribution and regulation of DC subtypes following multiple trauma. The main goal of this study was to assess whether the normal distribu- tion of circulating DC subpopulations is altered dur- ing the first 5 d after multiple trauma. Patients and methods. Sixty-three patients with mul- tiple trauma (ISS 31  15 points) and 11 healthy vol- unteers (control group) were enrolled. Blood samples were taken on admission (D0) and daily for the follow- ing 5 d. The percentages of MDC and PDC were deter- mined by flow cytometry. Results. A significant decline of the MDC concentra- tion was observable on days 3 to 5 after admission in comparison to the values obtained on the day of admis- sion. The ratio of MDC to PDC decreased significantly (3-fold, P < 0.05). This reduction correlated significantly with changes observed in the plasma concentrations of IL-10 (r  0.5; P < 0.05). Discussion. Our data demonstrate that multiple trauma is followed by a marked change in the sub- population composition of the DC compartment, and that these changes are inversely associated with en- hanced IL-10 plasma concentrations. This imbalance in the DC compartment favoring PDC concentrations may contribute to the immunological alterations that are observed following multiple trauma. © 2009 Elsevier Inc. All rights reserved. Key Words: dendritic cell; myeloid dendritic cell; MDC; plasmacytoid dendritic cell; PDC; multiple tra- uma; migration, apoptosis; IL-10. INTRODUCTION Multiple trauma is often accompanied by severe im- mune dysfunction. The initial inflammatory reaction can be triggered by bacterial infections or in response to cellular injury, hypoxia, hypo- and hyperthermia, and reperfusion injury [1, 2]. It has previously been shown that dendritic cells (DC) act as antigen present- ing cells and contribute to the initiation of the innate immune response concurrently with the activation of monocytes/macrophages. The activated DC and macro- phages are also believed to release various proinflam- matory cytokines such as IL-1, IL-6, TNF-, and other cytokines including IL-12, IL-15, IL-18, as well as chemokines [3]. Following cytokine expression, re- active oxygen species (ROS) and lipid mediators are released, and cellular adhesion molecules are up- regulated. These released mediators often lead to cap- illary leakage with cell swelling and to a severe distur- bance of the coagulation cascade, resulting in the deposition of fibrin clots in small vessel and subse- quently to an aggravation of tissue perfusion and organ failure [4]. Concomitant with the onset of inflamma- tion, a more prolonged counter-inflammatory response is initiated that attempts to restore immunological equilibrium and leads to impaired immune function, including the deactivation of macrophages, reduced anti- gen presentation, T-cell anergy, shift to a T-helper type-2 (Th2) response, and up-regulation of anti-inflammatory mediators (IL-10, IL-1Ra, sTNF-R) [5, 6]. 1 To whom correspondence and reprint requests should be ad- dressed at Klinik für Unfall-, Hand- und Wiederherstellungschirur- gie, Universitätsklinikum, Theodor-Stern-Kai 7, 60596 Frankfurt, Germany. E-mail: d.henrich@trauma.uni-frankfurt.de. Journal of Surgical Research 154, 239 –245 (2009) doi:10.1016/j.jss.2008.06.038 239 0022-4804/09 $36.00 © 2009 Elsevier Inc. All rights reserved.