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Title: Immunomodulatory effects of surgical trauma and blood transfusion
Author: Gharehbaghian, Ahmad
ISNI:       0000 0001 3495 7618
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2002
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Major surgical trauma and allogeneic transfusions cause immunomodulation, a systemic condition characterised by a reduction in natural killer (NK) cell function, macrophage migration, antigen presentation, proinflammatory cytokine synthesis and lymphocyte blastogenesis. Clinically there is increased tumour recurrence, increased post-operative infections, delayed wound healing, prolonged hospital stay and increased mortality. Immunomodulation affects innate immunity as reflected in NK cell function. Hence a method was developed to measure the NK cell precursor frequency (NKpf) in samples of peripheral blood mononuclear cells (PBMC). The technique was based on the principle of limiting dilution analysis and was performed in the presence of recombinant interleukin two (rIL-2) and rIL-15. After five day's culture lysis of the K562 cell-line was measured and NKpf calculated. NKpf was measured before and after joint replacement surgery in 120 orthopaedic patients assigned to five groups according to the type of transfused blood they received, namely: allogeneic non-Ieukodepleted; allogeneic leukodepleted; autologous unwashed blood salvaged post-operatively from the operation site (autologous salvaged), and autologous pre-deposit. The fifth group was non-transfused. Interferon-gamma (IFNy), IL-10 and IL-4 synthesis were measured in supernatants of similar cultures and flow-cytometry was used to measure percentage of the CD3 negative cells that were CD56 positive in the five-day cultures. The results showed all groups had significantly decreased post-operative NKpf (p<0.05), and non significant decreased post-operative IFNy and IL-10 synthesis (p>0.05) except the autologous salvaged group. By contrast, the latter showed a significant rise in post-operative NKpf values (p<0.05) and a non significant increase in IFNy and IL-10 synthesis (p>0.05). IL-4 and immunophenotyping studies were inconclusive. The proportion developing postoperative infections in those who received allogeneic blood (non-Ieukodepleted and leukodepleted) was 15% compared to 80/0 in those who received autologous blood (pre-deposit and salvaged) and 12% in the non-transfused group. It was concluded that, major surgical trauma could be associated with impairment of NK cell potential, decreased IFNy and IL-10 synthesis and that allogeneic transfusions add to these effects even after leukodepletion. These effects could lead to an increased risk of post-operative infections. By contrast autologous salvaged blood reverses these systemic effects perhaps by transferring locally synthesised cytokines and chemokines from the operation site to the circulation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available