Major gastrointestinal (GI) surgery promotes a specific gene expression pattern that upregulates the anti-inflammatory cytokine interleukin (IL)-10 while depressing proinflammatory immune pathways. Blood transfusions likely exacerbate this immune response, which also is associated with an increase in infectious complications. The finding raises the possibility that risk stratification for postoperative complications might use immunologic factors for prediction.
Immune response to a major physiologic insult includes an early proinflammatory phase, known as the systemic inflammatory response syndrome, which is then followed by an anti-inflammatory phase, known as the compensatory anti-inflammatory response syndrome (N Engl J Med 2003;348:138-150). Noting that the evidence supporting these two phases is scant and that more recent data have questioned its accuracy—especially in patients with severe sepsis or blunt trauma (Nat Rev Immunol 2013;13:862-874)—a group of investigators from Barts and The London School of Medicine and Dentistry as well as Bloomsbury Institute of Intensive Care Medicine at University College, London, undertook an analysis of gene expression in patients having major GI surgery.
All patients were aged over 45 years and were examined daily for the presence of infection (Table). Packed red blood cell (PRBC) transfusions were used because, unlike the effect of whole blood transfusions on postoperative infections, the immunologic consequence of leukocyte-depleted, PRBC transfusions is not well defined. The investigators, whose principal author was Paraskevi Fragkou, MBBS, hypothesized that major GI surgery will provoke an early postoperative immunosuppressive pattern of gene expression that will increase susceptibility to infectious complications. They also surmised that the transfusions themselves might contribute to immunosuppression in these surgical patients.
Table. Patient Demographics
Infection (n=44; 37%) No Infection (n=75; 63%) P Value
Age, y 66 (range, 59-75) 64 (56-71) 0.19
Male, % 61 63 1.0
Diabetes, % 18 16 0. 80
Current smokers, % 23 19 0.64
Smoking history, % 48 57 0.34
Cancer diagnosis, % 55 71 0. 10
Preoperative immunosuppression, % 14 14 1.0
Duration of operation, min 243 (range, 176-313) 195 (142-295) 0.06
Endoscopic surgery, % 18 32 0.13
Planned post-op ICU admission, % 77 66 0.22
ASA grade 3 or 4, % 30 31 1.0
By Surgical Specialty, n
General 4 5 –
Upper GI 9 18 –
Colorectal 18 31 –
HPB 11 19 –
HPB + colorectal 1 2 –
General + colorectal 1 0 0.84
Intraoperative blood transfusion 14 5 0.17
Blood transfusion in the last 24 h, % 23 7 0.02
In-hospital death, % 1 2 1.0
Blood was collected preoperatively and at 24 and 48 hours postoperatively. Messenger RNA (mRNA) was extracted and mediators descriptive of specified T-cell pathways were quantified by polymerase chain reaction.
The analysis of blood transfusion and immune pathways revealed a distinctive gene expression pattern. Foxp3, IL-12, IL-23, GATA3, RORgt and tumor necrosis factor (TNF)α/IL-10 mRNA levels were lower in those receiving blood transfusions in the first 24 hours postoperatively. Foxp3, IL-23, RORgt and TNFα/IL-10 mRNA levels were also lower at 48 hours postoperatively. IL-27 mRNA levels were unaffected by blood transfusion.
The authors, who presented their results at Euroanaesthesia 2014 (abstracts 1AP4-2 and 6AP2-1), found that mortality was associated with higher IL-10 mRNA levels at 48 hours, lower levels of IL-23 mRNA at 24 and 48 hours, and lower levels of RORgt mRNA at 48 hours.
They concluded that patients receiving blood transfusions were more likely to develop infectious complications and pneumonia, and were more likely to die in hospital. They found that blood transfusions during and after major GI surgery were “associated with a distinctive gene expression pattern that includes a dramatic upregulation of the anti-inflammatory cytokine IL-10.”