Aspects on the cytokine load in trauma with special reference to blood components and local versus systemic cytokine activity

Abstract: ASPECTS ON THE CYTOKINE LOAD IN TRAUMA with special reference to BLOOD COMPONENTS and LOCAL VERSUS SYSTEMIC CYTOKINE ACTIVITY by Marianne Kristiansson, M.D. Dissertation from the Department of Anaesthesiology and Intensive Care, Huddinge University Hospital Karolinska Institute, Stockholm and Department of Clinical Immunology, Umeå University Hospital, Umeå, Sweden Cytokines and their inhibitors are thought to be involved in many of the pathophysiological changes associated with trauma and infection. Therapeutic measures such as transfusion of blood components could have a bearing on the systemic cytokine load in these conditions. The relationship between local wound and systemic cytokine activity in humans has not been elucidated. The aims were to investigate the cytokine pattern in infected and not infected patients in the early postoperative period and the local and systcmic responses to trauma as reflected by the cytokine network and coagulation/fibrinolysis parameters and to characterize the content of cytokines in retrieved blood and in stored red blood cell concentrates (RBCs). Material and Methods: Activation of the immune system was assessed by determining the concentrations of ~he following components: tumour necrosis factor a (TNF), interleukin-l B (IL-I), interleukin-2 (IL-2), interleukin-6 (IL-6). interleukin-8 (IL-8), interleukin-10 (IL-10), soluble TNF receptors I and 11 (sTNF-R 1, sTNF-R 11), IL- I receptor antagonist (IL- I ra), a soluble form of the IL-6 receptor (slL-6-R). soluble E-Selectin (sE-Selectin), soluble intercellular adhesion molecule-l (slCAM 1), and soluble vascular adhesion molecule- I (sVCAM-I). Haemostatic mechanisms were assessed by determining thrombin-antithrombin complexes, fibrin, soluble, antithrombin, fibrin D-dimer, prothrombin fragment l+ 2, protein C and protein S. Tbe systemic proinflammatory cytokines were studied in 20 patients subjected to moderate or major surgery, 9 with infections and 11 without. The local and systemic immune/haemostatic responses were studied in 10 patients undergoing hip arthroplasty. The charactersistics of blood retrieved from a local tMuma site were investigated in 10 patients undergoing arthroplasty (hip or knee). Twenty-two units of stored RBCs were examined during the storage period. The effects of leukocyte filtration on the content of cytokines and soluble TNF receptors in RBCs were studied . Results: Patients with infections had higher IL-6 concentrations than those without. Interindividual variations of the plasma IL-6 concentrations were great in both groups. Wound drainage blood from a local trauma site hl patients undergoing arthroplasty displayed a more marked activation of the immune system, - in particular the anti-inflammatory components -, and of the haemostatic mechanisms than did the systemic circulation. In retrieved blood, intended for autotransfusion, marked hypercoagulability and increased concentrations of IL-6 were found. In stored RBCs, the concentrations of IL- I and IL-8 increased during the storage period. IL-2 was never detected. The concentrations of cytokines and solublc TNF receptors were higher in non-filtered than in prestorage filtered units of RBCs. Filtration at the end of the storage period did not affect the concentrations of cytohnes and soluble TNF receptors. Conclusions: The present data suggest that monitoring of the systemic concentrations of components of the cytokine network does not accurately reflect the local immune response. The amount of retrieved blood retransfused to patients ought to be considered. Stored RBCs contained cytokines, but we remain about the clinical implications of this finding. Prestorage leukocyte filtration reduced the occurrence of cytokines and soluble TNF receptors in RBCs which may suggest that the handling of blood components should be modified accordingly. Key words: Autotransfusion; Coagulation; Cytokines; Cytokine inhibitors; Fibrinolysis; Infection; Red blood cell concentrates; Surgery; Trauma. Stockholm 1997 ISBN 91-628-2367-1