Transfusion Medicine, 2011, 21, 236–246 doi: 10.1111/j.1365-3148.2011.01075.x ORIGINAL ARTICLE The effect of RBC transfusions on cytokine gene expression after cardiac surgery in patients developing post-operative multiple organ failure L. S. Sitniakowsky, 1 A. F. L. Later, 2 L. M. G. van de Watering, 1 M. Bogaerts, 1 A. Brand, 1,3 R. J. M. Klautz, 2 N. P. M. Smit 4 & J. A. van Hilten 1 1 Department of Transfusion Medicine, Sanquin Blood Supply, Research Division, 2 Department of Cardiothoracic Surgery, LUMC 3 Department of Immunohematology and Blood Transfusion, LUMC, and 4 Department of Clinical Chemistry, LUMC, Leiden, The Netherlands Received 28 September 2010; accepted for publication 23 February 2011 SUMMARY Aim: To determine the effect of red blood cell (RBC) transfusions during cardiac surgery on cytokine gene expression (GE) in relation to multiple organ fail- ure (MOF) development after systemic inflammatory response syndrome (SIRS). Background: RBC transfusion in cardiac surgery patients is dose-dependently associated with post- operative MOF, possibly acting as a second hit after cardiopulmonary bypass. Methods: For this observational study, 29 patients divided into four groups of cardiac surgery patients were selected from a randomised controlled trial (RCT). Group 1: no-RBC, no-MOF (N = 8); group 2: MOF, no-RBC (N = 7); group 3: RBC, no-MOF (N = 6); group 4: RBC and MOF (N = 8). Selection was based on age, gender, number of (leukocyte-depleted) RBC transfusions, type and duration of surgery. A 114 cytokine GE array was applied to blood samples withdrawn before and 24 h after surgery. Expression of selected genes was confirmed with reverse transcriptase real time-polymerase chain reaction (RT-PCR). Results: Nineteen of the 39 detectable genes showed a significant change in GE after surgery. Confirmed by RT- PCR, transfused MOF patients exhibit significantly less downregulation of CD40 ligand than control patients. Patients who would develop MOF show significantly larger increases in GE of transforming growth factor- α (TGF-α), tumour necrosis factor (TNF)-superfamily members 10 and 13B (TNFsf10/13B). Conclusions: When tested at 24 h after surgery, cytokine GE in peripheral blood leucocytes showed no significant differences between those transfused and those not transfused. Some alterations were seen in those developing MOF compared to those who did not, but the findings offer no role of leukocyte depleted (LD) RBC transfusion in the development of MOF. Key words: cardiac surgery; cytokines; gene expression; multiple organ failure; RBC transfusion. After cardiothoracic surgery using cardiopulmonary bypass (CPB), the majority of patients develop a systemic inflammatory response syndrome (SIRS) (Asimakopoulos et al., 1999). In a minority of patients this evolves into post-operative multiple organ failure (MOF) (Kollef et al.,1995). However, the pathogenesis of MOF still remains unclear. Various studies linking cytokines and organ failure have been performed in the Correspondence: Laura S. Sitniakowsky, Department of Transfusion Medicine, Sanquin Blood Supply, Division Research, Plesmanlaan 1a, Leiden 2333 BZ, The Netherlands. Tel.: +31 70 568 50 32; fax: +31 70 568 51 91; e-mail: L.Sitnyakowsky@sanquin.nl cardiothoracic surgery setting. Plasma levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β , sIL-2R, IL-8, IL-10, IL-12, IL-18, granulocyte monocyte colony stimulating factor (GM-CSF), TGF-beta and IL-6 were reported to be increased in patients with MOF, whereas IL-2 levels were lower compared with controls (Mei et al., 2007). In patients who developed MOF, IL-8 and IL-18 were increased in non-survivors (Sablotzki et al., 2002). Cardiac surgery with CPB with or without transfusions induces a pro- and anti-inflammatory cytokine cascade and plasma cytokine levels may rather reflect the phase of this cascade than be a cause of subsequent complica- tions in the patient (Aiboshi et al., 2001). © 2011 The Authors 236 Transfusion Medicine © 2011 British Blood Transfusion Society